Metabotropic glutamate subtype 5 receptors are quantified in human brain with a novel ligand 11C-SP203

415 Objectives Metabotropic glutamate receptor subtype 5 (mGluR5) is one of G-protein coupled receptors linked to many neuropsychiatric disorders. To our knowledge, only 11C-ABP688 has been used in humans as a 11C-labeled ligand, and it showed low levels of binding. We aimed to develop a new PET ligand, 11C-SP203, based on the identical structure of 18F-SP203, which previously showed high uptake in human brain. To assess the utility of 11C-SP203, we studied whole body distribution, feasibility of quantification in both volume of interest (VOI) and voxel data in healthy humans. Methods Dynamic whole body (n=8) and brain (n=6) scans were performed after bolus injection of 640 ± 99 MBq 11C-SP203. In whole body scans, radiation-absorbed doses were estimated by MIRD method. In all brain scans, distribution volume, (VT; mL/cm3) was measured using metabolite-corrected arterial input function by one- (1C) and two-compartment (2C) models for VOI data and by Logan and MA1 methods for voxel data. Results Effective dose based on whole body scans was 4.4 µSv/MBq, which was similar to that of other 11C radioligands. Brain scans showed high peak uptake (~6-7 SUV). 2C gave excellent VT identifiability (~2.5% SE) and fitted data better than 1C. Regional VT values ranged from 30 in temporal cortex to 10 in cerebellum. VT by 2C calculated from 60 and 120 min data differed by Conclusions 11C-SP203 is a promising radioligand for quantifying mGluR5 in human brain. The effective dose in humans is low and this can allow multiple scans in each subject on the same day. The high brain uptake makes voxel-based modeling feasible. Voxel-based MA1 provided accurate VT, and this method is appropriate to use in future studies to compare healthy controls and patient populations.