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

Overview

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.

Interventions

• Drug 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).

Primary outcome measures

• Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects [Time frame: Baseline]
• Number of participants with adverse events related to tracer administration as assessed by CTCAE v4.0 [Time frame: 5 years]

Secondary outcome measures (2)

• Binding of 18-F 3F4AP in brain lesions of multiple sclerosis subjects [Time frame: Baseline]
• Within-subject variability in healthy controls and multiple sclerosis subjects [Time frame: Retest within 3 months of baseline]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• Massachusetts General Hospital — Boston

Publications

• 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. 2026 Jan;53(2):1125-1138. doi: 10.1007/s00259-025-07454-1. Epub 2025 Aug 5. PMID 40759830

Identifiers

NCT: NCT04699747 · 2020P002459

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗