SV2A PET Imaging in Healthy Subjects and Epilepsy Patients

The first goal of this proposal is to fully validate 11C UCB J for human use to quantify SV2A. The second goal is to determine age effects on SV2A in vivo. Application of this tracer in neurodegenerative diseases will require a careful understanding of normal age-related changes in synaptic density. The third goal is to assess SV2A density in epilepsy patients (EP).

We will execute this study through the following Specific Aims:
Aim 1: To conduct tracer validation studies with bolus/infusion delivery including test/retest studies and in vivo specificity studies of 11C UCB J. In Aim 1A, 12 healthy young subjects will undergo two test/retest 11C UCB J scans on the High Resolution Research Tomography (HRRT). In Aim 1B, 8 additional subjects will undergo a 2-scan test/block paradigm with LEV administered IV. Data from these studies will define the optimal scanning protocol, the appropriate quantitative method to derive VT, the reproducibility of kinetic parameters, and the nondisplaceable volume of distribution (VND) to calculate binding potential (BPND).

Aim 2: To evaluate the age dependency of SV2A in healthy subjects. In Aim 2A, 16 older subjects will be studied with 11C UCB J. In Aim 2B, 8 additional older subjects will be studied using the test/block paradigm with LEV. Thus, we will evaluate age-dependent changes in total and specific binding of 11C UCB J (n=16+8=24). MR-based partial volume correction will be performed to eliminate effects of cortical atrophy.
Aim 3: To examine SV2A density in epilepsy patients. We will compare 11C UCB J binding in 24 EP to age- and sex-matched healthy controls (from Aims 1 and 2). We hypothesize that in vivo imaging of 11C UCB J will reveal decreased SV2A binding in the epileptogenic regions of the brain. 11C UCB J binding will also be compared to that of 18F FDG in the same patients; we believe that 11C UCB J has the potential to be more diagnostically useful than 18F FDG for seizure focus determination in EP.