[carbonyl-11C]4-Fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([11C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain

Introduction: Metabotropic glutamate subtype receptor 1 (mGluR1) is implicated in several neuropsychiatric disorders and is a target for drug development. [F-18]FIMX ([F-18]4-fluoro-N-methyl-N-(4-(6-(methylamino) pyrimidin-4-yl)thiazol-2-yl)benzamide) is an effective radioligand for imaging brain mGluR1 with PET. A similarly effective radioligand with a shorter half-life would usefully allow PET studies of mGluR1 at baseline and after pharmacological or other challenge on the same day. Here we describe the preparation of [C-11]FIMX for evaluation in monkey with PET. Methods: [C-11]FIMX was prepared via Pd-promoted carbonylation of 1-fluoro-4-iodobenzene with [C-11]carbon monoxide, aminolysis of the [C-11]acyl-palladium complex with the requisite Boc-protected amine, and deprotection with HCl in THF. PET scans of [C-11]FIMX injected into a monkey were performed at baseline and after preblock of mGluR1 with measurement of the arterial input function. Results: The radiosynthesis required 42 min and gave [C-11]FIMX in about 5% overall decay-corrected radiochemical yield and with a specific activity of about 100 GBq/mu mol. PET in rhesus monkey at baseline showed that radioactivity peaked high in receptor-rich cerebellum and much lower in receptor-poor occipital cortex. Radioactivity in cerebellum declined to 32% of peak at 85 min. V-T at baseline appeared stable in all brain regions after 60 min. Under mGluR1 pre-blocked condition, radioactivity uptake in all regions declined more rapidly to a low level. Receptor pre-block reduced V-T from 13.0 to 1.5 in cerebellum and from 2.9 to 1.4 in occipital cortex. Conclusion: [C-11]FIMX is an effective radioligand for imaging mGluR1 in monkey with PET. Published by Elsevier Inc.