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

Обзор

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.

Вмешательства

• Препарат 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).

Первичные конечные точки

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

Вторичные конечные точки (2)

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

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Massachusetts General Hospital — Boston

Публикации

• 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

Идентификаторы

NCT: NCT04699747 · 2020P002459

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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