Investigating the Utility of Demyelination Tracer [18F]3F4AP in Controls and Multiple Sclerosis Subjects

NCT ID: NCT04699747

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-25
• Study Completion Date: 2026-11-30

Brief Summary

Our overall objective is to obtain an initial assessment of the potential value of using [18F]3F4AP for imaging demyelinating diseases such as multiple sclerosis:

• Aim 1) Assess the safety of [18F]3F4AP in healthy volunteers and subjects with multiple sclerosis (MS). Hypothesis 1: Administration of [18F]3F4AP will result in no changes in vitals or other adverse events.
• Aim 2) Assess the pharmacokinetics of a bolus infusion of [18F]3F4AP in humans including healthy volunteers and MS patients. Hypothesis 2: the pharmacokinetics of [18F]3F4AP at the whole brain level will be similar in controls and MS subjects. The kinetics in demyelinated lesions will be slower than in healthy control areas.
• Aim 3) Assess the reproducibility of [18F]3F4AP in humans. Hypothesis 3: the test/retest variability of [18F]3F4AP within the same subject will be lower than 10%.
• Aim 4) Correlate MR brain images with [18F]3F4AP PET brain images. Hypothesis 4A: all the lesions seen on the MRI will show increased signal (VT or SUV) on the PET images. Hypothesis 4B: some of the lesions on the MRI will show increased signal (VT or SUV) on the PET but not all.
• Aim 5) Correlate [18F]3F4AP PET signal with neuropsychological testing in people with MS. Hypothesis 5: increased PET signal (VT or SUV) will correlate with impaired Single Digit Modality Test (SDMT) scores.
• Aim 6) Correlate [18F]3F4AP PET signal with EDSS score in people with MS. Hypothesis 6: increased PET signal (VT or SUV) will correlate with higher EDSS scores.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Multiple sclerosis

F-18 3F4AP PET Scan

Group Type: EXPERIMENTAL

F-18 3F4AP

Intervention Type: DRUG

Subjects will be injected once per imaging session (a maximum of 2 imaging sessions) with up to 10 mCi (±20%) of 18-F 3F4AP as a rapid intravenous bolus (within 1 min).

Healthy controls

F-18 3F4AP PET Scan

Group Type: ACTIVE_COMPARATOR

F-18 3F4AP

Intervention Type: DRUG

Subjects will be injected once per imaging session (a maximum of 2 imaging sessions) with up to 10 mCi (±20%) of 18-F 3F4AP as a rapid intravenous bolus (within 1 min).

Interventions

F-18 3F4AP

Subjects will be injected once per imaging session (a maximum of 2 imaging sessions) with up to 10 mCi (±20%) of 18-F 3F4AP as a rapid intravenous bolus (within 1 min).

Intervention Type: DRUG

Other Intervention Names

[18F]3F4AP

Eligibility Criteria

Inclusion Criteria

• Subjects must be ≥18 and <65 years of age;
• Able to understand and provide informed consent prior to study procedures

Exclusion Criteria

• Subjects with known structural brain disease (e.g. brain tumor or stroke);
• Any contraindication to MRI and/or PET, including:

• Subjects with life vest;
• Subjects with implanted heart device (e.g. ICD, Pacemaker);
• Subjects with metallic fragment or foreign body;
• Subjects with other form of devices or prosthesis that are not MRI compatible, such as insulin pump, joint replacement, hearing aid, cochlear implant, permanent contraceptive devices, etc.;
• Subjects with severe claustrophobia
• Relative or absolute contraindication to Dotarem contrast:
• history of renal disease including acute or chronic severe renal insufficiency (glomerular filtration rate <60 mL/min/1.73m2);
• history of diabetes mellitus, systemic lupus, multiple myeloma, nephrogenic systemic fibrosis, and other co-morbidities;
• History of hypersensitive reactions to Dotarem and/or gadolinium contrast agent;
• Radiation exposure exceeds current Radiology Department guidelines (i.e., 50 mSv in the prior 12 months);
• Female subjects only: Positive serum pregnancy test, or lactating, or possibility of pregnancy cannot be ruled out prior to dosing;
• Inability to provide written informed consent;
• Any clinically significant acute or unstable physical or psychiatric condition, judged by the investigators based on medical history or screening physical examination, to be incompatible with the study;
• Any physical or psychiatric condition judged by the investigators to be incompatible with the study, based on medical history or screening physical examination;
• Abnormal results on blood tests judged by the investigators to be incompatible with the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Pedro Brugarolas

Assistant Professor of Radiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Pedro Brugarolas, PhD

Role: CONTACT

pbrugarolas@mgh.harvard.edu

(617) 643-4574

Facility Contacts

Pedro Brugarolas, PhD

Role: primary

617-643-4574

References

Tiss A, Michaelson NM, Russo AW, Ramos-Torres KM, Sun Y, DaSilva NE, Noel JM, Liu F, Gong K, Huang SY, Popko B, Baker S, Klawiter EC, Brugarolas P. First evaluation in multiple sclerosis using PET tracer [18F]3F4AP demonstrates heterogeneous binding across lesions. Eur J Nucl Med Mol Imaging. 2025 Aug 5. doi: 10.1007/s00259-025-07454-1. Online ahead of print.

Reference Type: DERIVED

PMID: 40759830 (View on PubMed)

Other Identifiers

2020P002459

Identifier Type: -

Identifier Source: org_study_id