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

Purpose

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.

Condition

  • Multiple Sclerosis

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Intervention Model Description
Drug: F-18 3F4AP PET scan
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Multiple sclerosis 		F-18 3F4AP PET Scan
  • 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).
    Other names:
    • [18F]3F4AP
Active Comparator
Healthy controls 		F-18 3F4AP PET Scan
  • 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).
    Other names:
    • [18F]3F4AP

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Pedro Brugarolas, PhD
617-643-4574

More Details

Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

Pedro Brugarolas, PhD
(617) 643-4574
pbrugarolas@mgh.harvard.edu