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

NCT04699747 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2020P002459
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Keywords

Demyelination; Brain imaging; Positron Emission Tomography; Radiopharmaceutical

Outcome Measures

Primary Outcomes (2)

• Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects

  Binding of the tracer will be quantified using volumes of distribution (VTs). Volume of distribution is the ratio of tracer concentration in tissue to plasma at equilibrium and will be determined using standard pharmacokinetic methods (Innis et al, J Cereb Blood Flow Metab. 2007; 27(9): 1533-1539).

  Baseline

• Number of participants with adverse events related to tracer administration as assessed by CTCAE v4.0

  Determine number of participants adverse events related to tracer administration as assessed by CTCAE v4.0

  5 years

Secondary Outcomes (2)

• Binding of 18-F 3F4AP in brain lesions of multiple sclerosis subjects

  Baseline

• Within-subject variability in healthy controls and multiple sclerosis subjects

  Retest within 3 months of baseline

Study Arms (2)

Multiple sclerosis

EXPERIMENTAL

F-18 3F4AP PET Scan

Drug: F-18 3F4AP

Healthy controls

ACTIVE COMPARATOR

F-18 3F4AP PET Scan

Drug: F-18 3F4AP

Interventions

F-18 3F4AP 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).

Also known as: [18F]3F4AP

Healthy controls; Multiple sclerosis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 40759830 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Demyelinating Diseases

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Pedro Brugarolas, PhD

CONTACT

(617) 643-4574; pbrugarolas@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Radiology

Model Details: Drug: F-18 3F4AP PET scan

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: January 7, 2021
• Study Start: March 25, 2021
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)