Radiosynthesis and evaluation of 5-methyl-N-(4-[C-11]methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine ([C-11]ADX88178) as a novel radioligand for imaging of metabotropic glutamate receptor subtype 4 (mGluR4)

摘要

ADX88178 (1) has been recently developed as a potent positive allosteric modulator for metabotropic glutamate receptor 4 (mGluR4). The aim of this study was to develop [C-11]1 as a novel positron emission tomography ligand and to evaluate its binding ability for mGluR4. Using stannyl precursor 3, [C-11]1 was efficiently synthesized by introducing an [C-11]methyl group into a pyrimidine ring via C-C-11 coupling and deprotection reactions, in 16 +/- 6% radiochemical yield (n = 10). At the end of synthesis, 0.54-1.10 GBq of [C-11]1 was acquired with > 98% radiochemical purity and 90-120 GBq/mu mol of specific activity. In vitro autoradiography and ex vivo biodistribution study in rat brains showed specific binding of [C-11]1 in the cerebellum, striatum, thalamus, cerebral cortex, and medulla oblongata, which showed dose-dependent decreases by administration with multi-dose of unlabeled 1. (C) 2015 Elsevier Ltd. All rights reserved.