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.

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.