Trial Outcomes & Findings for Evaluating Safety of Escalating Doses of Tilmanocept by IV Injection and SPECT Imaging in Subjects With and Without RA (NCT NCT02865434)

NCT ID: NCT02865434

Last Updated: 2021-08-12

Results Overview

Number of participants that experienced pharmacologic activity or ADR in each dose group.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 39 participants
• Primary outcome timeframe: From Enrollment to termination, up to 53 days
• Results posted on: 2021-08-12

Participant Flow

Participant milestones

Measure	Group 1 (RA) Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Overall Study STARTED	3	3	3	3	3	3	3	3	3	6	6
Overall Study COMPLETED	3	3	3	3	3	3	3	3	3	6	6
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluating Safety of Escalating Doses of Tilmanocept by IV Injection and SPECT Imaging in Subjects With and Without RA

Baseline characteristics by cohort

Measure	Group 1 (RA) n=3 Participants Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) n=3 Participants Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) n=3 Participants Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) n=3 Participants Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) n=3 Participants Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) n=3 Participants Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) n=3 Participants Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) n=3 Participants Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) n=3 Participants Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Total n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=8 Participants	3 Participants n=8 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	6 Participants n=42 Participants	6 Participants n=42 Participants	39 Participants n=42 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Continuous	55.3 years STANDARD_DEVIATION 8.14 • n=5 Participants	58.7 years STANDARD_DEVIATION 4.73 • n=7 Participants	55.0 years STANDARD_DEVIATION 11.16 • n=5 Participants	46.3 years STANDARD_DEVIATION 9.87 • n=4 Participants	50.7 years STANDARD_DEVIATION 12.74 • n=21 Participants	52.0 years STANDARD_DEVIATION 12.53 • n=8 Participants	53.3 years STANDARD_DEVIATION 5.69 • n=8 Participants	56.3 years STANDARD_DEVIATION 8.14 • n=24 Participants	58.0 years STANDARD_DEVIATION 3.00 • n=42 Participants	32.0 years STANDARD_DEVIATION 12.55 • n=42 Participants	55.0 years STANDARD_DEVIATION 11.16 • n=42 Participants	54.2 years STANDARD_DEVIATION 8.99 • n=42 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=8 Participants	3 Participants n=8 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants	30 Participants n=42 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants	9 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants	3 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=8 Participants	3 Participants n=8 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	6 Participants n=42 Participants	4 Participants n=42 Participants	36 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=8 Participants	2 Participants n=8 Participants	2 Participants n=24 Participants	1 Participants n=42 Participants	3 Participants n=42 Participants	5 Participants n=42 Participants	26 Participants n=42 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants	2 Participants n=42 Participants	1 Participants n=42 Participants	9 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	3 participants n=21 Participants	3 participants n=8 Participants	3 participants n=8 Participants	3 participants n=24 Participants	3 participants n=42 Participants	6 participants n=42 Participants	6 participants n=42 Participants	39 participants n=42 Participants
BMI	24.4 kg/m^2 STANDARD_DEVIATION 7.4 • n=5 Participants	29.8 kg/m^2 STANDARD_DEVIATION 3.10 • n=7 Participants	33.5 kg/m^2 STANDARD_DEVIATION 7.5 • n=5 Participants	29.5 kg/m^2 STANDARD_DEVIATION 8.47 • n=4 Participants	39.2 kg/m^2 STANDARD_DEVIATION 11.75 • n=21 Participants	39.3 kg/m^2 STANDARD_DEVIATION 8.80 • n=8 Participants	29.2 kg/m^2 STANDARD_DEVIATION 4.76 • n=8 Participants	34.5 kg/m^2 STANDARD_DEVIATION 4.62 • n=24 Participants	33.5 kg/m^2 STANDARD_DEVIATION 6.37 • n=42 Participants	27.3 kg/m^2 STANDARD_DEVIATION 7.74 • n=42 Participants	33.5 kg/m^2 STANDARD_DEVIATION 7.5 • n=42 Participants	32.7 kg/m^2 STANDARD_DEVIATION 7.72 • n=42 Participants

PRIMARY outcome

Timeframe: From Enrollment to termination, up to 53 days

Number of participants that experienced pharmacologic activity or ADR in each dose group.

Outcome measures

Measure	Group 1 (RA) n=3 Participants Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) n=3 Participants Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) n=3 Participants Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) n=3 Participants Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) n=3 Participants Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) n=3 Participants Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) n=3 Participants Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) n=3 Participants Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) n=3 Participants Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Incidence of Adverse Drug Reaction	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	6 Participants	6 Participants	—	—

SECONDARY outcome

Timeframe: For Groups 1-9, 60 ± 15 min or 180 ± 15 minute post injection planar and SPECT/CT images are used

Population: Subjects enrolled in Groups 10 and 11 received whole-body planar scans following Tc99 administration for PK and dosimetry analyses only.

Tc 99m Tilmanocept localization is defined as the visually (i.e., qualitatively) determined binary categorization of Tc 99m tilmanocept activity in a given DAS28 joint. The purpose of the visual assessments is to obtain dichotomized classifications of tracer uptake (herein referenced as 'localization') on planar images. Per subject localization rate is the number of subjects with at least one localized DAS28 joint per number of subjects in the analysis population.

Outcome measures

Measure	Group 1 (RA) n=3 Participants Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) n=3 Participants Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) n=3 Participants Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) n=3 Participants Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) n=3 Participants Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) n=3 Participants Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) n=3 Participants Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) n=3 Participants Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) n=3 Participants Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Per Subject Localization Rate of Tc 99m Tilmanocept by SPECT Imaging 180 ± 15 min	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	—	—	—	—
Per Subject Localization Rate of Tc 99m Tilmanocept by SPECT Imaging 60 ± 15 min	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	—	—	—	—

SECONDARY outcome

Timeframe: Whole-body planar scan at 60 ± 15 and 180 ± 15 minutes post Tc 99m tilmanocept administration with a duration of approximately 25 to 30 minutes at each timepoint.

Population: Groups 10 \& 11 were not included in the population these endpoints were evaluated for.

Per joint (clinically RA-identified) joint localization rate of Tc 99m tilmanocept is defined as the number of localized joints per number of joints from subjects in the analysis population Groups 1-9 using SPECT imaging.

Outcome measures

Measure	Group 1 (RA) n=23 Joint Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) n=82 Joint Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) n=45 Joint Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) n=32 Joint Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) n=13 Joint Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) n=52 Joint Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) n=16 Joint Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) n=24 Joint Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) n=29 Joint Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Tc 99m Tilmanocept Joint Localization Rate in Rheumatoid Arthritis Identified Joints Joint localization at 1 hr	7 Joint	40 Joint	25 Joint	12 Joint	5 Joint	28 Joint	5 Joint	13 Joint	12 Joint	0 Joint	0 Joint	—	—
Tc 99m Tilmanocept Joint Localization Rate in Rheumatoid Arthritis Identified Joints Joint localization at 3 hr	16 Joint	42 Joint	20 Joint	20 Joint	8 Joint	24 Joint	11 Joint	11 Joint	17 Joint	—	—	—	—

SECONDARY outcome

Timeframe: Qualitative (i.e., visual) assessments of planar images were acquired at the 60 ± 15-minute and 180 ± 15-minute timepoints in Groups 1-9.

Population: Groups 10 \& 11 were not included in the population these endpoints were evaluated for.

Concordance is defined as the relationship or the presence of Tc99m localization in anatomical areas of active RA defined by clinical symptomology (defined as joint swelling (SJC) and/or tenderness (TJC) during the screening DAS28 evaluation).

Outcome measures

Measure	Group 1 (RA) n=59 Joint Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) n=64 Joint Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) n=44 Joint Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) n=78 Joint Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) n=62 Joint Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) n=60 Joint Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) n=67 Joint Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) n=97 Joint Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) n=63 Joint Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Concordance Concordance at 1 hr	21 Joint	32 Joint	17 Joint	39 Joint	31 Joint	29 Joint	30 Joint	53 Joint	35 Joint	0 Joint	0 Joint	—	—
Concordance Concordance at 3 hr	38 Joint	32 Joint	27 Joint	39 Joint	31 Joint	31 Joint	37 Joint	44 Joint	28 Joint	0 Joint	0 Joint	—	—

SECONDARY outcome

Timeframe: Post-injection imaging at 60±15 and 180±15 min

Population: Groups 1-9 only. Groups 10 and 11 were not included.

Localization intensity is defined as the presence of Tc99m in each DAS28 joint and is output in tilmanocept uptake value (TUV) units, as computed using the following equation:

〖TUV〗=ROI/BRAIN×100 where ROI = decay-corrected avg voxel intensity of the joint ROI and BRAIN =decay-corrected avg voxel intensity of the brain RR

Outcome measures

Measure	Group 1 (RA) n=28 Joints Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) n=28 Joints Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) n=28 Joints Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) n=28 Joints Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) n=28 Joints Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) n=28 Joints Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) n=3 Participants Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) n=3 Participants Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) n=3 Participants Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Localization Intensity 180 ± 15 min L MCP1	527.8 TUV Standard Deviation 355.31	309.9 TUV Standard Deviation 57.82	293.9 TUV Standard Deviation 93.47	321.2 TUV Standard Deviation 169.11	300.3 TUV Standard Deviation 136.28	216.6 TUV Standard Deviation 17.24	259.7 TUV Standard Deviation 56.52	297.4 TUV Standard Deviation 107.98	327.7 TUV Standard Deviation 58.96	—	—	—	—
Localization Intensity 180 ± 15 min R Knee	92.5 TUV Standard Deviation 39.11	126.5 TUV Standard Deviation 47.90	124.0 TUV Standard Deviation 40.28	122.1 TUV Standard Deviation 40.79	105.3 TUV Standard Deviation 23.75	76.5 TUV Standard Deviation 11.68	107.5 TUV Standard Deviation 37.05	191.4 TUV Standard Deviation 180.37	151.8 TUV Standard Deviation 25.49	—	—	—	—
Localization Intensity 60 ± 15 min R PIP5	107.9 TUV Standard Deviation 13.12	174.7 TUV Standard Deviation 59.35	88.9 TUV Standard Deviation 54.01	144.3 TUV Standard Deviation 66.00	104.0 TUV Standard Deviation 33.68	104.3 TUV Standard Deviation 29.19	186.8 TUV Standard Deviation 36.75	170.9 TUV Standard Deviation 91.39	170.5 TUV Standard Deviation 103.26	—	—	—	—
Localization Intensity 60 ± 15 min L Elbow	68.3 TUV Standard Deviation 3.38	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	76.6 TUV Standard Deviation NA Result from 2 of 3 group participants not available due to joint being outside of image field of view.	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	104.7 TUV Standard Deviation 22.16	82.3 TUV Standard Deviation 15.04	72.1 TUV Standard Deviation 4.87	—	—	—	—
Localization Intensity 60 ± 15 min R Elbow	87.4 TUV Standard Deviation 4.94	88.4 TUV Standard Deviation NA Result from 2 of 3 group participants not available due to joint being outside of image field of view.	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	94.7 TUV Standard Deviation 19.29	76.5 TUV Standard Deviation NA Result from 2 of 3 group participants not available due to joint being outside of image field of view.	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	110.3 TUV Standard Deviation 14.34	101.1 TUV Standard Deviation 16.15	77.3 TUV Standard Deviation 13.07	—	—	—	—
Localization Intensity 60 ± 15 min L Wrist	292.7 TUV Standard Deviation 96.46	415.9 TUV Standard Deviation 55.06	332.7 TUV Standard Deviation 168.46	416.1 TUV Standard Deviation 202.00	246.3 TUV Standard Deviation 109.90	358.4 TUV Standard Deviation 136.55	387.4 TUV Standard Deviation 157.13	472.9 TUV Standard Deviation 386.02	368.8 TUV Standard Deviation 146.85	—	—	—	—
Localization Intensity 60 ± 15 min L MCP4	181.0 TUV Standard Deviation 40.41	374.9 TUV Standard Deviation 103.52	204.7 TUV Standard Deviation 78.91	225.3 TUV Standard Deviation 93.15	214.8 TUV Standard Deviation 93.50	185.5 TUV Standard Deviation 50.83	253.1 TUV Standard Deviation 61.97	240.9 TUV Standard Deviation 221.84	211.7 TUV Standard Deviation 75.61	—	—	—	—
Localization Intensity 60 ± 15 min L MCP5	141.9 TUV Standard Deviation 28.51	323.4 TUV Standard Deviation 77.01	159.4 TUV Standard Deviation 67.15	207.1 TUV Standard Deviation 87.17	206.5 TUV Standard Deviation 101.51	166.2 TUV Standard Deviation 34.36	236.1 TUV Standard Deviation 42.07	220.3 TUV Standard Deviation 152.82	220.9 TUV Standard Deviation 59.92	—	—	—	—
Localization Intensity 60 ± 15 min R MCP2	231.7 TUV Standard Deviation 26.52	405.4 TUV Standard Deviation 153.35	285.8 TUV Standard Deviation 106.50	295.1 TUV Standard Deviation 227.83	188.6 TUV Standard Deviation 58.65	272.7 TUV Standard Deviation 183.37	286.7 TUV Standard Deviation 46.46	269.6 TUV Standard Deviation 167.41	286.1 TUV Standard Deviation 114.89	—	—	—	—
Localization Intensity 60 ± 15 min R MCP 3	245.8 TUV Standard Deviation 19.43	353.6 TUV Standard Deviation 45.80	237.7 TUV Standard Deviation 135.01	296.9 TUV Standard Deviation 156.42	229.1 TUV Standard Deviation 72.37	234.8 TUV Standard Deviation 122.53	267.8 TUV Standard Deviation 44.47	323.9 TUV Standard Deviation 288.11	336.0 TUV Standard Deviation 158.66	—	—	—	—
Localization Intensity 60 ± 15 min R MCP4	224.4 TUV Standard Deviation 20.27	326.4 TUV Standard Deviation 59.57	189.9 TUV Standard Deviation 102.96	231.4 TUV Standard Deviation 147.10	223.3 TUV Standard Deviation 78.82	242.7 TUV Standard Deviation 143.34	259.0 TUV Standard Deviation 62.48	265.8 TUV Standard Deviation 137.12	290.5 TUV Standard Deviation 133.03	—	—	—	—
Localization Intensity 60 ± 15 min R MCP5	182.3 TUV Standard Deviation 4.68	316.1 TUV Standard Deviation 109.30	153.9 TUV Standard Deviation 85.85	208.0 TUV Standard Deviation 140.89	162.2 TUV Standard Deviation 53.15	192.0 TUV Standard Deviation 69.35	219.6 TUV Standard Deviation 86.83	222.1 TUV Standard Deviation 117.16	215.5 TUV Standard Deviation 103.57	—	—	—	—
Localization Intensity 60 ± 15 min L PIP3	125.7 TUV Standard Deviation 7.78	212.3 TUV Standard Deviation 93.24	117.0 TUV Standard Deviation 58.62	170.1 TUV Standard Deviation 105.66	129.8 TUV Standard Deviation 65.39	120.2 TUV Standard Deviation 12.47	201.1 TUV Standard Deviation 48.49	204.0 TUV Standard Deviation 160.22	200.3 TUV Standard Deviation 85.58	—	—	—	—
Localization Intensity 60 ± 15 min L PIP4	109.6 TUV Standard Deviation 8.41	172.9 TUV Standard Deviation 20.07	106.9 TUV Standard Deviation 43.54	151.8 TUV Standard Deviation 56.55	126.3 TUV Standard Deviation 58.40	117.5 TUV Standard Deviation 24.73	163.8 TUV Standard Deviation 53.06	215.6 TUV Standard Deviation 152.95	171.4 TUV Standard Deviation 75.27	—	—	—	—
Localization Intensity 60 ± 15 min L PIP5	95.2 TUV Standard Deviation 14.68	126.3 TUV Standard Deviation 38.80	86.6 TUV Standard Deviation 23.94	138.5 TUV Standard Deviation 89.37	108.9 TUV Standard Deviation 66.64	96.4 TUV Standard Deviation 13.92	149.5 TUV Standard Deviation 54.15	215.6 TUV Standard Deviation 183.50	160.8 TUV Standard Deviation 36.56	—	—	—	—
Localization Intensity 60 ± 15 min R PIP1	165.5 TUV Standard Deviation 6.81	285.6 TUV Standard Deviation 51.59	141.7 TUV Standard Deviation 71.45	171.3 TUV Standard Deviation 71.34	152.8 TUV Standard Deviation 48.86	148.7 TUV Standard Deviation 6.24	208.5 TUV Standard Deviation 39.27	244.8 TUV Standard Deviation 154.04	239.4 TUV Standard Deviation 74.89	—	—	—	—
Localization Intensity 60 ± 15 min L Knee	66.5 TUV Standard Deviation 17.79	107.4 TUV Standard Deviation 38.98	79.5 TUV Standard Deviation 18.89	101.4 TUV Standard Deviation 23.40	79.6 TUV Standard Deviation 15.84	78.5 TUV Standard Deviation 32.65	86.8 TUV Standard Deviation 14.06	176.7 TUV Standard Deviation 170.34	124.0 TUV Standard Deviation 16.81	—	—	—	—
Localization Intensity 180 ± 15 min R Shoulder	189.1 TUV Standard Deviation 51.36	240.5 TUV Standard Deviation 118.56	230.0 TUV Standard Deviation 81.69	209.3 TUV Standard Deviation 86.04	177.6 TUV Standard Deviation 54.82	148.9 TUV Standard Deviation 12.60	221.6 TUV Standard Deviation 59.4	321.0 TUV Standard Deviation 237.86	206.1 TUV Standard Deviation 41.31	—	—	—	—
Localization Intensity 180 ± 15 min R elbow	85.5 TUV Standard Deviation 7.77	97.3 TUV Standard Deviation NA Result from 2 of 3 group participants not available due to joint being outside of image field of view.	85.9 TUV Standard Deviation NA Result from 2 of 3 group participants not available due to joint being outside of image field of view.	109.3 TUV Standard Deviation 44.46	71.2 TUV Standard Deviation NA Result from 2 of 3 group participants not available due to joint being outside of image field of view.	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	102.1 TUV Standard Deviation 28.42	94.3 TUV Standard Deviation 4.39	90.9 TUV Standard Deviation 5.49	—	—	—	—
Localization Intensity 180 ± 15 min L Wrist	401.8 TUV Standard Deviation 201.69	488.6 TUV Standard Deviation 40.47	434.0 TUV Standard Deviation 183.81	514.7 TUV Standard Deviation 275.68	299.7 TUV Standard Deviation 126.01	404.1 TUV Standard Deviation 126.88	457.9 TUV Standard Deviation 157.64	566.6 TUV Standard Deviation 374.43	484.7 TUV Standard Deviation 164.36	—	—	—	—
Localization Intensity 180 ± 15 min R Wrist	387.6 TUV Standard Deviation 246.92	479.7 TUV Standard Deviation 73.26	482.2 TUV Standard Deviation 169.64	582.1 TUV Standard Deviation 411.89	404.5 TUV Standard Deviation 177.65	465.1 TUV Standard Deviation 269.97	565.6 TUV Standard Deviation 283.40	534.7 TUV Standard Deviation 314.36	456.8 TUV Standard Deviation 194.99	—	—	—	—
Localization Intensity 180 ± 15 min L MCP2	259.7 TUV Standard Deviation 67.37	378.4 TUV Standard Deviation 212.17	404.1 TUV Standard Deviation 168.75	316.1 TUV Standard Deviation 114.50	252.7 TUV Standard Deviation 139.89	225.7 TUV Standard Deviation 30.86	300.6 TUV Standard Deviation 157.04	364.3 TUV Standard Deviation 184.71	237.1 TUV Standard Deviation 131.01	—	—	—	—
Localization Intensity 180 ± 15 min L MCP3	252.3 TUV Standard Deviation 60.46	456.5 TUV Standard Deviation 90.38	327.1 TUV Standard Deviation 97.70	317.3 TUV Standard Deviation 184.41	302.4 TUV Standard Deviation 146.85	220.4 TUV Standard Deviation 63.17	393.1 TUV Standard Deviation 57.80	364.2 TUV Standard Deviation 210.61	300.5 TUV Standard Deviation 84.15	—	—	—	—
Localization Intensity 180 ± 15 min L MCP4	219.8 TUV Standard Deviation 44.10	414.3 TUV Standard Deviation 76.72	273.5 TUV Standard Deviation 71.29	278.8 TUV Standard Deviation 139.18	261.5 TUV Standard Deviation 128.77	195.4 TUV Standard Deviation 39.10	361.9 TUV Standard Deviation 60.33	315.2 TUV Standard Deviation 195.40	305.5 TUV Standard Deviation 97.92	—	—	—	—
Localization Intensity 180 ± 15 min L MCP5	179.8 TUV Standard Deviation 59.65	413.1 TUV Standard Deviation 81.96	203.2 TUV Standard Deviation 61.46	264.4 TUV Standard Deviation 165.09	251.9 TUV Standard Deviation 128.70	184.4 TUV Standard Deviation 44.55	276.4 TUV Standard Deviation 62.35	298.0 TUV Standard Deviation 104.10	228.8 TUV Standard Deviation 43.52	—	—	—	—
Localization Intensity 180 ± 15 min R MCP1	298.9 TUV Standard Deviation 68.07	344.3 TUV Standard Deviation 25.68	284.4 TUV Standard Deviation 68.47	351.1 TUV Standard Deviation 222.79	288.4 TUV Standard Deviation 127.85	258.6 TUV Standard Deviation 71.85	346.9 TUV Standard Deviation 33.49	356.0 TUV Standard Deviation 64.44	416.8 TUV Standard Deviation 194.14	—	—	—	—
Localization Intensity 180 ± 15 min R MCP2	289.9 TUV Standard Deviation 37.14	495.1 TUV Standard Deviation 256.02	341.6 TUV Standard Deviation 126.66	405.0 TUV Standard Deviation 343.20	271.4 TUV Standard Deviation 146.89	300.3 TUV Standard Deviation 147.97	294.3 TUV Standard Deviation 40.20	397.0 TUV Standard Deviation 170.33	340.5 TUV Standard Deviation 169.41	—	—	—	—
Localization Intensity 180 ± 15 min R MCP3	320.9 TUV Standard Deviation 76.70	428.1 TUV Standard Deviation 5.42	286.9 TUV Standard Deviation 118.06	404.0 TUV Standard Deviation 242.78	300.1 TUV Standard Deviation 171.48	298.2 TUV Standard Deviation 138.42	330.5 TUV Standard Deviation 97.94	385.2 TUV Standard Deviation 256.76	367.9 TUV Standard Deviation 121.03	—	—	—	—
Localization Intensity 180 ± 15 min R MCP4	263.6 TUV Standard Deviation 24.44	380.8 TUV Standard Deviation 38.83	271.1 TUV Standard Deviation 101.92	320.0 TUV Standard Deviation 202.62	284.2 TUV Standard Deviation 137.20	271.2 TUV Standard Deviation 73.89	255.3 TUV Standard Deviation 56.27	361.8 TUV Standard Deviation 223.67	363.7 TUV Standard Deviation 104.49	—	—	—	—
Localization Intensity 180 ± 15 min R MCP5	214.5 TUV Standard Deviation 37.25	373.2 TUV Standard Deviation 122.41	218.4 TUV Standard Deviation 67.7	276.1 TUV Standard Deviation 168.15	262.1 TUV Standard Deviation 140.52	187.3 TUV Standard Deviation 34.76	270.6 TUV Standard Deviation 58.95	332.5 TUV Standard Deviation 162.83	369.2 TUV Standard Deviation 77.77	—	—	—	—
Localization Intensity 180 ± 15 min L PIP1	179.4 TUV Standard Deviation 41.32	270.7 TUV Standard Deviation 98.35	177.0 TUV Standard Deviation 76.74	220.4 TUV Standard Deviation 125.71	224.0 TUV Standard Deviation 146.46	156.1 TUV Standard Deviation 8.23	206.3 TUV Standard Deviation 25.63	275.1 TUV Standard Deviation 74.03	254.3 TUV Standard Deviation 95.16	—	—	—	—
Localization Intensity 180 ± 15 min L PIP2	144.4 TUV Standard Deviation 12.55	165.9 TUV Standard Deviation 44.85	151.2 TUV Standard Deviation 38.91	209.8 TUV Standard Deviation 116.11	189.5 TUV Standard Deviation 106.68	142.4 TUV Standard Deviation 18.60	227.5 TUV Standard Deviation 50.02	285.4 TUV Standard Deviation 229.72	204.8 TUV Standard Deviation 63.14	—	—	—	—
Localization Intensity 180 ± 15 min L PIP3	152.4 TUV Standard Deviation 45.18	257.6 TUV Standard Deviation 126.40	157.8 TUV Standard Deviation 72.64	215.3 TUV Standard Deviation 120.83	160.7 TUV Standard Deviation 81.29	155.2 TUV Standard Deviation 54.09	224.2 TUV Standard Deviation 5.85	285.6 TUV Standard Deviation 241.39	204.4 TUV Standard Deviation 84.03	—	—	—	—
Localization Intensity 180 ± 15 min L PIP4	133.6 TUV Standard Deviation 22.67	185.2 TUV Standard Deviation 10.12	150.9 TUV Standard Deviation 48.91	195.7 TUV Standard Deviation 120.38	167.2 TUV Standard Deviation 96.27	157.8 TUV Standard Deviation 28.39	249.7 TUV Standard Deviation 77.85	246.4 TUV Standard Deviation 191.83	198.6 TUV Standard Deviation 85.67	—	—	—	—
Localization Intensity 180 ± 15 min L PIP5	104.1 TUV Standard Deviation 17.04	151.0 TUV Standard Deviation 25.51	124.2 TUV Standard Deviation 27.15	191.1 TUV Standard Deviation 149.39	143.7 TUV Standard Deviation 98.53	109.1 TUV Standard Deviation 16.35	219.4 TUV Standard Deviation 95.36	183.6 TUV Standard Deviation 85.21	168.3 TUV Standard Deviation 58.47	—	—	—	—
Localization Intensity 180 ± 15 min R PIP2	193.0 TUV Standard Deviation 43.56	204.7 TUV Standard Deviation 18.16	174.8 TUV Standard Deviation 67.84	256.4 TUV Standard Deviation 140.51	187.3 TUV Standard Deviation 75.12	164.9 TUV Standard Deviation 57.27	211.9 TUV Standard Deviation 56.41	200.5 TUV Standard Deviation 47.74	225.4 TUV Standard Deviation 9.65	—	—	—	—
Localization Intensity 180 ± 15 min R PIP3	182.4 TUV Standard Deviation 14.8	224.8 TUV Standard Deviation 21.69	164.0 TUV Standard Deviation 64.36	239.6 TUV Standard Deviation 135.40	184.9 TUV Standard Deviation 76.62	198.0 TUV Standard Deviation 85.74	255.0 TUV Standard Deviation 65.78	263.1 TUV Standard Deviation 120.11	229.3 TUV Standard Deviation 44.24	—	—	—	—
Localization Intensity 180 ± 15 min R PIP4	164.6 TUV Standard Deviation 30.74	376.6 TUV Standard Deviation 103.08	175.3 TUV Standard Deviation 78.67	213.4 TUV Standard Deviation 147.22	170.3 TUV Standard Deviation 97.90	182.8 TUV Standard Deviation 47.32	243.5 TUV Standard Deviation 36.60	292.8 TUV Standard Deviation 174.85	196.2 TUV Standard Deviation 108.71	—	—	—	—
Localization Intensity 180 ± 15 min R PIP5	125.7 TUV Standard Deviation 8.97	200.3 TUV Standard Deviation 73.56	119.7 TUV Standard Deviation 30.65	181.4 TUV Standard Deviation 90.31	148.5 TUV Standard Deviation 64.16	117.3 TUV Standard Deviation 44.55	147.5 TUV Standard Deviation 47.18	233.4 TUV Standard Deviation 102.14	197.7 TUV Standard Deviation 50.77	—	—	—	—
Localization Intensity 180 ± 15 min L Knee	80.5 TUV Standard Deviation 26.70	113.8 TUV Standard Deviation 39.80	104.5 TUV Standard Deviation 27.67	126.1 TUV Standard Deviation 43.18	98.6 TUV Standard Deviation 25.98	87.5 TUV Standard Deviation 37.21	101.2 TUV Standard Deviation 32.64	193.7 TUV Standard Deviation 177.10	146.8 TUV Standard Deviation 22.71	—	—	—	—
Localization Intensity 60 ± 15 min R Wrist	387.6 TUV Standard Deviation 246.92	420.9 TUV Standard Deviation 59.76	351.3 TUV Standard Deviation 139.75	458.5 TUV Standard Deviation 282.25	271.9 TUV Standard Deviation 88.55	432.4 TUV Standard Deviation 268.22	465.5 TUV Standard Deviation 254.62	492.0 TUV Standard Deviation 351.80	337.6 TUV Standard Deviation 191.93	—	—	—	—
Localization Intensity 60 ± 15 min L MCP1	192.2 TUV Standard Deviation 5.81	299.2 TUV Standard Deviation 51.36	203.1 TUV Standard Deviation 64.07	230.2 TUV Standard Deviation 97.52	222.9 TUV Standard Deviation 81.58	186.0 TUV Standard Deviation 18.29	241.4 TUV Standard Deviation 41.31	250.7 TUV Standard Deviation 95.14	326.9 TUV Standard Deviation 123.01	—	—	—	—
Localization Intensity 60 ± 15 min L PIP1	130.4 TUV Standard Deviation 5.02	239.3 TUV Standard Deviation 91.26	127.2 TUV Standard Deviation 48.94	196.6 TUV Standard Deviation 98.77	148.4 TUV Standard Deviation 53.25	134.8 TUV Standard Deviation 21.00	201.2 TUV Standard Deviation 113.75	166.8 TUV Standard Deviation 100.57	243.9 TUV Standard Deviation 14.08	—	—	—	—
Localization Intensity 60 ± 15 min L PIP2	120.7 TUV Standard Deviation 14.68	158.4 TUV Standard Deviation 55.78	105.4 TUV Standard Deviation 49.80	153.3 TUV Standard Deviation 72.08	129.8 TUV Standard Deviation 55.88	126.0 TUV Standard Deviation 17.08	177.9 TUV Standard Deviation 18.887	129.9 TUV Standard Deviation 41.93	165.6 TUV Standard Deviation 46.37	—	—	—	—
Localization Intensity 60 ± 15 min L Shoulder	138.9 TUV Standard Deviation 27.35	193.2 TUV Standard Deviation 85.82	188.4 TUV Standard Deviation 92.19	177.9 TUV Standard Deviation 64.22	135.0 TUV Standard Deviation 31.90	146.1 TUV Standard Deviation 35.54	177.6 TUV Standard Deviation 19.37	269.3 TUV Standard Deviation 238.60	152.7 TUV Standard Deviation 37.92	—	—	—	—
Localization Intensity 60 ± 15 min R Shoulder	156.1 TUV Standard Deviation 19.95	222.6 TUV Standard Deviation 113.08	181.2 TUV Standard Deviation 73.69	179.5 TUV Standard Deviation 65.66	145.7 TUV Standard Deviation 26.65	140.8 TUV Standard Deviation 12.82	180.1 TUV Standard Deviation 18.23	293.8 TUV Standard Deviation 255.64	184.8 TUV Standard Deviation 17.51	—	—	—	—
Localization Intensity 60 ± 15 min R PIP3	156.6 TUV Standard Deviation 6.02	189.6 TUV Standard Deviation 18.21	124.5 TUV Standard Deviation 74.14	215.0 TUV Standard Deviation 127.88	140.7 TUV Standard Deviation 30.08	168.1 TUV Standard Deviation 95.49	191.8 TUV Standard Deviation 43.07	224.3 TUV Standard Deviation 141.68	189.5 TUV Standard Deviation 44.79	—	—	—	—
Localization Intensity 60 ± 15 min R PIP4	133.2 TUV Standard Deviation 19.03	200.5 TUV Standard Deviation 83.90	125.4 TUV Standard Deviation 99.16	161.3 TUV Standard Deviation 93.41	143.0 TUV Standard Deviation 53.77	143.6 TUV Standard Deviation 57.59	160.7 TUV Standard Deviation 50.81	221.6 TUV Standard Deviation 161.97	156.8 TUV Standard Deviation 47.62	—	—	—	—
Localization Intensity 60 ± 15 min R Knee	76.2 TUV Standard Deviation 23.25	118.8 TUV Standard Deviation 50.05	99.3 TUV Standard Deviation 36.85	98.3 TUV Standard Deviation 22.13	78.7 TUV Standard Deviation 14.07	67.1 TUV Standard Deviation 8.62	91.1 TUV Standard Deviation 14.44	165.4 TUV Standard Deviation 174.57	133.7 TUV Standard Deviation 22.82	—	—	—	—
Localization Intensity 180 ± 15 min L Shoulder	165.4 TUV Standard Deviation 54.95	210.1 TUV Standard Deviation 89.77	232.2 TUV Standard Deviation 116.41	211.0 TUV Standard Deviation 81.71	160.8 TUV Standard Deviation 55.63	163.0 TUV Standard Deviation 37.4	218.0 TUV Standard Deviation 67.76	301.4 TUV Standard Deviation 254.58	181.4 TUV Standard Deviation 66.68	—	—	—	—
Localization Intensity 180 ± 15 min L Elbow	71.8 TUV Standard Deviation 13.49	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	76.2 TUV Standard Deviation NA Result from 2 of 3 group participants not available due to joint being outside of image field of view.	102.4 TUV Standard Deviation 49.11	57.7 TUV Standard Deviation NA Result from 2 of 3 group participants not available due to joint being outside of image field of view.	NA TUV Standard Deviation NA Result from all 3 group participants not available due to joint being outside of image field of view.	94.6 TUV Standard Deviation 13.84	101.2 TUV Standard Deviation 25.92	91.0 TUV Standard Deviation 2.59	—	—	—	—
Localization Intensity 60 ± 15 min L MCP2	175.1 TUV Standard Deviation 23.18	394.3 TUV Standard Deviation 152.28	318.7 TUV Standard Deviation 148.66	243.8 TUV Standard Deviation 101.78	177.0 TUV Standard Deviation 80.29	167.6 TUV Standard Deviation 43.83	333.5 TUV Standard Deviation 68.95	323.6 TUV Standard Deviation 263.03	248.3 TUV Standard Deviation 132.40	—	—	—	—
Localization Intensity 60 ± 15 min L MCP3	187.1 TUV Standard Deviation 28.12	408.7 TUV Standard Deviation 64.48	259.4 TUV Standard Deviation 118.16	228.7 TUV Standard Deviation 123.51	206.7 TUV Standard Deviation 87.69	187.9 TUV Standard Deviation 44.78	286.5 TUV Standard Deviation 26.59	324.0 TUV Standard Deviation 258.57	270.5 TUV Standard Deviation 122.88	—	—	—	—
Localization Intensity 60 ± 15 min R MCP1	238.0 TUV Standard Deviation 31.29	310.8 TUV Standard Deviation 41.45	230.0 TUV Standard Deviation 73.68	261.1 TUV Standard Deviation 155.97	254.9 TUV Standard Deviation 78.65	226.3 TUV Standard Deviation 57.31	261.6 TUV Standard Deviation 27.81	354.4 TUV Standard Deviation 162.04	349.4 TUV Standard Deviation 213.53	—	—	—	—
Localization Intensity 60 ± 15 min R PIP2	137.5 TUV Standard Deviation 12.17	184.6 TUV Standard Deviation 33.97	121.7 TUV Standard Deviation 61.52	194.8 TUV Standard Deviation 97.92	139.7 TUV Standard Deviation 56.90	133.3 TUV Standard Deviation 49.95	215.1 TUV Standard Deviation 35.17	198.1 TUV Standard Deviation 144.14	187.0 TUV Standard Deviation 77.42	—	—	—	—
Localization Intensity 180 ± 15 min R PIP1	218.6 TUV Standard Deviation 53.24	309.0 TUV Standard Deviation 60.52	202.1 TUV Standard Deviation 67.80	221.3 TUV Standard Deviation 133.90	222.0 TUV Standard Deviation 117.48	194.1 TUV Standard Deviation 32.36	303.2 TUV Standard Deviation 62.42	261.8 TUV Standard Deviation 138.92	262.7 TUV Standard Deviation 83.66	—	—	—	—

SECONDARY outcome

Timeframe: Imaging taken 60 ± 15 min and 180 ± 15 min post-injection

Population: Only Groups 1-9. Groups 10 \& 11 were not included in the population these endpoints were evaluated for.

Per subject localization rate of Tc 99m tilmanocept in areas other than RA is defined as the number of subjects with at least one localized DAS28 joint per number of subjects in the analysis population.

Outcome measures

Measure	Group 1 (RA) n=3 Participants Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) n=3 Participants Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) n=3 Participants Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) n=3 Participants Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) n=3 Participants Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) n=3 Participants Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) n=3 Participants Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) n=3 Participants Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) n=3 Participants Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Per Subject Localization Rate of Tc 99m Tilmanocept in Areas Other Than RA Number of subjects localized at 60 ± 15 min	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	—	—	—	—
Per Subject Localization Rate of Tc 99m Tilmanocept in Areas Other Than RA Number of subjects localized at 180 ± 15 min	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	—	—	—	—

SECONDARY outcome

Timeframe: 15 minutes prior to administration. Immediately after administration. 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration

Population: Only in Groups 10 and 11

Maximum observed concentration (Cmax) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.

Outcome measures

Measure	Group 1 (RA) Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Maximum Observed Concentration (Cmax)	—	—	—	—	—	—	—	—	—	1244.2 nCi/mL Interval 809.55 to 1649.33	2043.8 nCi/mL Interval 1078.28 to 2878.94	—	—

SECONDARY outcome

Timeframe: Radioactivity was quantitated at each time point -15 mins prior to administration• Immediately after administration •15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post admi

Population: Groups 10 and 11

Time to Cmax (tmax) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.

Outcome measures

Measure	Group 1 (RA) Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Time to Cmax (Tmax)	—	—	—	—	—	—	—	—	—	27.3 minutes Standard Deviation 7.36	255 minutes Standard Deviation 6.58	—	—

SECONDARY outcome

Timeframe: Hour 0 to hour 18-20, with time points immediately post injection, 0.25 hr, 1 hr, 3 hr and 18-20 hr after injection

Population: Groups 10 and 11

Area under the concentration-time curve (AUC) from Hour 0 to the last measureable concentration (18 to 20 hours) (AUC0-t) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.

Outcome measures

Measure	Group 1 (RA) Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measureable Concentration (AUC0-t) Whole blood AUC	—	—	—	—	—	—	—	—	—	235258.0 min*nCi/mL Interval 193698.75 to 275134.27	268110.7 min*nCi/mL Interval 217187.41 to 316806.03	—	—
Area Under the Concentration-time Curve (AUC) From Hour 0 to the Last Measureable Concentration (AUC0-t) Urine AUC	—	—	—	—	—	—	—	—	—	1468788.9 min*nCi/mL Interval 1088888.09 to 1830437.75	1384642.0 min*nCi/mL Interval 1123310.11 to 1634810.07	—	—

SECONDARY outcome

Timeframe: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration

Population: Groups 10 and 11 only.

AUC extrapolated to infinity will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.

Outcome measures

Measure	Group 1 (RA) Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
AUC Extrapolated to Infinity	—	—	—	—	—	—	—	—	—	370580.1 min*nCi/mL Interval 290005.04 to 447777.17	396026.4 min*nCi/mL Interval 315475.79 to 472251.44	—	—

SECONDARY outcome

Timeframe: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration

Population: Groups 10 and 11 only.

Apparent terminal elimination rate constant (Z) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.

Outcome measures

Measure	Group 1 (RA) Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Apparent Terminal Elimination Rate Constant (Z)	—	—	—	—	—	—	—	—	—	0.00094 1/minute Interval 0.0008 to 0.00107	0.00100 1/minute Interval 0.00083 to 0.00116	—	—

SECONDARY outcome

Timeframe: 15 mins prior to administration • Immediately after administration • 15 ± 5 minutes post administration • 60 ± 15 minutes post administration • 180 ± 15 minutes post administration • 18 to 20 hours post administration

Population: Groups 10 and 11.

Apparent terminal elimination half-life (t1/2) will be calculated, whenever possible, using Tc 99m tilmanocept total radioactivity in whole blood and urine.

Outcome measures

Measure	Group 1 (RA) Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Apparent Terminal Elimination Half-life (t1/2)	—	—	—	—	—	—	—	—	—	759.0 minutes Interval 648.36 to 865.85	719.1 minutes Interval 598.97 to 835.46	—	—

SECONDARY outcome

Timeframe: Planar images were taken 15 ± 5 minutes, 60 ± 5 minutes, 180 ± 5 minutes, 18 to 20 hours after Tc 99m tilmanocept administration and processed in accordance with the NAV3-21 protocol endpoints using established dosimetry software.

Population: Groups 10 and 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection.

Mean total radiation dose per organ (mSv/MBq) in HC females, HC males, females with active RA, and males with active RA.

Results were obtained at the subject level from Hybrid Dosimetry™ Version 2.8.3 and OLINDA/EXM® Version 2.1RC93 in accordance with NAV3-21 Protocol Amendment 6. The Hybrid Dosimetry™ function provides an efficient way to generate kinetic data for selected organs via regions of interest (ROI) drawing. From this data, residence times are calculated and transferred to OLINDA/EXM®, which generates absorbed dose tables using the MIRD methodology.

Outcome measures

Measure	Group 1 (RA) Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=3 Participants Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=3 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Females) n=3 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA Males) n=3 Participants Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Radiation Dosimetry of Tc 99m Tilmanocept	—	—	—	—	—	—	—	—	—	4.69 mSv/MBq Standard Deviation 4.54	2.69 mSv/MBq Standard Deviation 1.13	5.06 mSv/MBq Standard Deviation 4.93	3.02 mSv/MBq Standard Deviation 2.97

Adverse Events

Group 1 (RA)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Group 2 (RA)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 3 (RA)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 4 (RA)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 5 (RA)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 6 (RA)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Group 7 (RA)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 8 (RA)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Group 9 (RA)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 10 (Healthy Controls)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Group 11 (RA)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Group 1 (RA) n=3 participants at risk Group 1 will receive 50 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m as a single IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 2 (RA) n=3 participants at risk Group 2 will receive 200 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 3 (RA) n=3 participants at risk Group 3 will receive 400 µg Tc99m-tilmanocept radiolabeled with 10 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 4 (RA) n=3 participants at risk Group 4 will receive 50 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 5 (RA) n=3 participants at risk Group 5 will receive 200 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 6 (RA) n=3 participants at risk Group 6 will receive 400 µg Tc99m-tilmanocept radiolabeled with 5 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 7 (RA) n=3 participants at risk Group 7 will receive 50 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 8 (RA) n=3 participants at risk Group 8 will receive 200 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 9 (RA) n=3 participants at risk Group 9 will receive 400 µg Tc99m-tilmanocept radiolabeled with 1 mCi Tc99m via IV injection. Subjects will receive SPECT Imaging (60 Minutes post-injection) and SPECT Imaging (180 Minutes post-injection). Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. SPECT Imaging (60 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 60 Minutes post-injection. SPECT Imaging (180 Minutes post-injection): Subjects enrolled in Groups 1-9 will receive whole body planar SPECT imaging with 3D SPECT or SPECT/CT for targeted joints of interest 180 Minutes post-injection. Planar Image with both Hands in Field of View: Subjects in Groups 1-9 and Groups 10 and 11 will receive planar imaging with both hands in the field of view at 60 and 180 minutes post-injection.	Group 10 (Healthy Controls) n=6 participants at risk Group 10 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m at the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).	Group 11 (RA) n=6 participants at risk Group 11 will receive the maximum tested dose of 400 mcg tilmanocept radiolabeled with 10 mCi of Tc 99m the MTD via IV injection. Tc99m-tilmanocept: Tilmanocept is a radiotracer that accumulates in macrophages by binding to a mannose binding receptor that resides on the surface. Whole body planar SPECT imaging (15 Minutes post-injection), Whole body planar SPECT imaging (60 minutes post-injection), Whole body planar SPECT imaging (180 minutes post-injection), and Whole body planar SPECT imaging (18-20 hours post-injection). Planar Image with both Hands in Field of View (60 minutes and 180 minutes post-injection). Blood Collection for PK Testing (15 Mins Before Injection), Blood Collection for PK Testing (after Injection), Blood Collection for PK Testing (15 minutes post injection), Blood Collection for PK Testing (60 minutes post injection), Blood Collection for PK Testing (180 minutes post injection), and Blood Collection for PK Testing (18-20 hours post injection).
Endocrine disorders Hypoglycemia	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/6 • 53 days	16.7% 1/6 • Number of events 1 • 53 days
Gastrointestinal disorders Nausea	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	16.7% 1/6 • Number of events 1 • 53 days	0.00% 0/6 • 53 days
Gastrointestinal disorders Vomiting	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	16.7% 1/6 • Number of events 1 • 53 days	0.00% 0/6 • 53 days
General disorders Fatigue	33.3% 1/3 • Number of events 1 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/6 • 53 days	0.00% 0/6 • 53 days
Infections and infestations Urinary Tract Infection	66.7% 2/3 • Number of events 2 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/6 • 53 days	0.00% 0/6 • 53 days
Skin and subcutaneous tissue disorders Blister	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	33.3% 1/3 • Number of events 1 • 53 days	0.00% 0/3 • 53 days	0.00% 0/6 • 53 days	0.00% 0/6 • 53 days
Skin and subcutaneous tissue disorders Dermatitis Contact	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	33.3% 1/3 • Number of events 1 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/3 • 53 days	0.00% 0/6 • 53 days	0.00% 0/6 • 53 days

Additional Information

Bonnie Abbruzzzese

Navidea Biopharmaceuticals

Phone: 6147937500

Email: babbruzzese@navidea.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and make modifications to the publication.
• Publication restrictions are in place

Restriction type: OTHER