Correlation Tween Fdg Pet For Neuronal Function And C-11-Ucb-J Pet For Synaptic Density Using Suv Ratios With Cerebellum Reference In Alzheimer'S Disease

422 Objectives: 11C-UCB-J is a specific PET ligand for synaptic vesicle glycoprotein 2A (SV2A) and has been proposed as a biomarker for synaptic density (1-3). Previously, we found significant reduction (~ 40%) of hippocampal SV2A binding in Alzheimer’s disease (AD) compared to age-matched cognitively normal (CN) participants (4). We also found an overall good correlation between synaptic density measured by 11C-UCB-J PET and neuronal function measured by FDG PET in the hippocampus and susceptible brain regions in the same AD and CN participants. Here we explore the use of the simplified quantitative method of SUV ratio (SUVR) to cerebellum reference for 11C-UCB-J in correlation with SUVR of FDG. Methods: Nine AD and 8 CN participants were enrolled for both 11C-UCB-J and FDG PET scans on the HRRT. AD participants were all confirmed Aβ+ by 11C-PiB and spanned the disease stages from amnestic mild cognitive impairment (MCI, n=4) to mild dementia (n=5). CN participants were all confirmed Aβ-. SUV images (60-90 min) were generated for both 11C-UCB-J and FDG PET. Multiple ROIs were taken using both AAL and FreeSurfer (FS) templates from individual MR images: hippocampus, caudate, putamen, thalamus, entorhinal, anterior and posterior cingulate, and frontal, temporal, parietal, and occipital cortices. Regional SUVRs were calculated with the cerebellum (CB) as reference region. Separate comparisons of regional SUVRs for 11C-UCB-J and FDG between AD and CN groups were performed with two-tailed, unpaired t-test with P Results: There was an excellent correlation between SUVs from FS and AAL templates in most cortical regions for both 11C-UCB-J and FDG (R=0.96-0.99), with the SUVs from FS segmented ROIs being higher than SUVs from AAL for both tracers. Using FS ROIs with CB reference, we found significant reduction of 11C-UCB-J SUVR in the hippocampus of AD compared to CN (16.0%, P 0.5 with P 0.05). The correlation values between 11C-UCB-J and FDG were larger than our previous findings using centrum semiovale white matter as reference. Conclusions: We demonstrated significant reduction of 11C-UCB-J SUVRs in the hippocampus, thalamus and posterior cingulate of AD participants. The simplified SUVRs for 11C-UCB-J PET with no arterial blood sampling could provide a reliable alternative for large scale clinical trials in AD. There was an overall better correlation between 11C-UCB-J and FDG using SUVRs with the same CB reference region, which could be due to lower noise from a larger reference region or artifactual correlation by using the same region. Further exploration in other projecting brain regions with partial volume correction in a large scale cohort study is needed to better elucidate these relationships and their significance in AD pathophysiology. Funding: The Dana Foundation, NIH P50AG047270, R01AG52560