Radiosynthesis and preliminary evaluation of 4-[18F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as a new positron emission tomography ligand for metabotropic glutamate receptor subtype 1

The purpose of this study was to develop 4-[18F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([18F]FITM, [18F]4) as a new PET ligand for imaging metabotropic glutamate receptor subtype 1 (mGluR1). [18F]4 was synthesized by [18F]fluorination of a novel nitro precursor 3 with [18F]KF in the presence of Kryptofix 222. At the end of synthesis, 429–936 MBq (n = 8) of [18F]4 was obtained with >99% radiochemical purity and 204–559 GBq/μmol specific activity starting from 6.7 to 13.0 GBq of [18F]F−. The brain distribution of [18F]4 was determined by the in vitro and ex vivo autoradiography using rat brain sections. The in vitro and in vivo specific binding of [18F]4 to mGluR1 was detected in the cerebellum, thalamus, hippocampus, and striatum. These results suggest that [18F]4 is a promising PET ligand for the in vivo evaluation of mGluR1.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide