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

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 Sv/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