investigating the utility of demyelination tracer [18f]3f4ap in controls and multiple sclerosis subjects

Conditions: Multiple Sclerosis

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.


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.

Keywords: demyelination brain imaging positron emission tomography radiopharmaceutical