18F-mFBG Cardiac Uptake With Lewy Body Dementia

NCT ID: NCT07176286

Last Updated: 2025-10-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2026-07-30

Brief Summary

This is a Phase 2 study evaluating the positron-emitting radiopharmaceutical 18F-mFBG as an imaging agent for quantification of the effect of neurodegenerative diseases on myocardial sympathetic innervation. Effectiveness of 18F-mFBG imaging of the heart will be judged in terms of the quantitative difference between results for subjects with Lewy body and non-Lewy body neurologic disease as compared to historical data for healthy control subjects.

Detailed Description

Over the past 40 years, significant efforts have been made to develop imaging techniques to monitor the heart's autonomic nervous system, particularly the sympathetic system and its key neurohormone, norepinephrine (NE). In heart disease, NE function is often disrupted, leading to reduced NE uptake and transporter expression, which can contribute to heart failure, arrhythmias, and sudden cardiac death. Similar NE system dysfunction is also seen in neurological conditions like pure autonomic failure (PAF), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB), which are associated with Lewy body deposits in the nervous system. Most research on myocardial sympathetic neuronal imaging has focused on NE-analogues labeled with gamma- or positron-emitting radioisotopes. The most commonly studied agent is 123I-mIBG, which provides semi-quantitative data. However, its results depend heavily on imaging equipment and techniques, making global standardization difficult. Additionally, accurately measuring myocardial uptake and clearance is challenging with SPECT, even when using correction methods. While most cardiac mIBG research has focused on patients with heart disease, a significant number of studies have examined the effect of Lewy body disease on myocardial sympathetic innervation. These studies have consistently demonstrated a significant reduction in myocardial mIBG uptake. mIBG scintigraphy has high sensitivity (88%) and specificity (85%) for distinguishing Parkinson's disease (PD) from other Parkinsonism disorders. In a study of 123I-mIBG scans, the heart/mediastinum ratio (HMR) showed 68.9% sensitivity and 89.1% specificity for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Neurologists and movement disorder specialists find mIBG imaging helpful for assessing suspected Lewy body disease. Positron-emission tomography (PET) is the preferred method for high-resolution imaging of cellular functions. This study uses 18F-meta-fluorobenzylguanidine (18F-mFBG), a new radiopharmaceutical similar in structure to 123I-mIBG but with faster pharmacokinetics and elimination. Compared to 123I-mIBG, 18F-mFBG clears more quickly from the blood and target organs, resulting in better heart imaging quality and reliability. While most research on 18F-mFBG has focused on imaging neural crest tumors like neuroblastoma and pheochromocytoma, its performance is expected to be strong based on prior experience with 123I-mIBG. With the greater sensitivity and resolution of PET imaging compared to planar and SPECT techniques, it is expected that 18F-mFBG imaging will be less procedure-dependent than 123I-mIBG and provide the reliable and reproducible quantitative accuracy necessary to support use of this agent for clinical patient studies.

Conditions

Parkinson Disease (PD); Lewy Body Dementia (LBD)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Cohort 1: Known or presumed Lewy body disease (Parkinson's disease (PD) and Lewy body dementia (LBD)

All subjects will receive an intravenous injection of 222-370 MBq (6-10 mCi) 18F-mFBG. At 30 minutes post-administration, whole-body imaging will be performed from the head to the pelvis. A static image of the thorax will be acquired at 60 minutes.

Group Type: ACTIVE_COMPARATOR

18F-MFBG

Intervention Type: DRUG

Intravenous injection of 222-370 MBq (6-10 mCi) 18F-mFBG followed by whole body PET imaging.

Cohort 2: neurologic disease due to non-Lewy body pathology.

All subjects will receive an intravenous injection of 222-370 MBq (6-10 mCi) 18F-mFBG. At 30 minutes post-administration, whole-body imaging will be performed from the head to the pelvis. A static image of the thorax will be acquired at 60 minutes.

Group Type: ACTIVE_COMPARATOR

18F-MFBG

Intervention Type: DRUG

Intravenous injection of 222-370 MBq (6-10 mCi) 18F-mFBG followed by whole body PET imaging.

Interventions

18F-MFBG

Intravenous injection of 222-370 MBq (6-10 mCi) 18F-mFBG followed by whole body PET imaging.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. ≥18 years of age at study entry. 2. Able and willing to comply with study procedures and signed and dated informed consent is obtained.

3. A male or a female who is either surgically sterile (has had a documented bilateral oophorectomy and/or hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom the result of a serum pregnancy test performed at screening is negative.

4. All subjects: Judged clinically stable for at least 30 days before enrolment into the study and remains stable to the time of the study imaging procedure.

For Lewy body disease subjects (Study Cohort I):

5. The subject has a diagnosis of either PD or DLB based on accepted clinical criteria at least 6 months before enrollment into the study.

For non-Lewy body disease subjects (Study Cohort II):

6. The subject has a diagnosis of neurological or neurodegenerative disease for which neither PD nor DLB is judged likely by a neurologist based on accepted clinical and imaging criteria.

Exclusion Criteria

• 1. Previously entered into this study or has participated in any other investigational product or medical device study within 30 days of enrollment.

2. History or suspicion of significant allergic reaction or anaphylaxis to any components of the 18F-mFBG imaging agent.

3. Presents with any other clinically active, serious, life-threatening disease with a life expectancy of less than 1 year or where participation in the study might compromise the management of the subject or other reason that in the judgment of the investigator(s) makes the subject unsuitable for participation in the study.

4. Documented ischemic heart disease (prior myocardial infarction, unstable angina, etc) or a diagnosis of heart failure of ischemic or non-ischemic etiology.

5. Serious non-cardiac medical condition associated with significant elevation of plasma catecholamines including pheochromocytoma.

6. The subject is claustrophobic or has a movement disorder that prevents him/her from lying still in a supine position for up to 20 minutes.

7. Renal insufficiency (serum creatinine >3.0 mg/dL). 8. Uses medications that are known to interfere with uptake of NET-dependent agents and these medications cannot be safely withheld 24 hours before study procedures.

9. Participated in a research study using ionizing radiation in the previous 12 months such that participation in the study might result in a total effective dose from research procedures exceeding 50 milliSieverts during that time interval.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innervate Radiopharmaceuticals LLC (Formerly: Illumina Radiopharmaceuticals LLC)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juan B Toledo, MD

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

Central Contacts

Research Coordinator

Role: CONTACT

Jrrodriguezgaytan@houstonmethodist.org

346-238-2677

Clinical Trials Manager

Role: CONTACT

Acalmaguerjuarez@houstonmethodist.org

346-238-1565

Other Identifiers

IRP101-231

Identifier Type: -

Identifier Source: org_study_id