Synthesis and in vitro evaluation of three novel radiotracers for imaging of metabotropic glutamate receptor subtype 2 in rat brain.

The purpose of this study was to develop three new radiotracers, 1-(cyclopropylmethyl)-4-([C/F]substituted-phenyl)piperidin-1-yl-2-oxo-1,2-dihydropyridine-3-carbonitrile ([C]1, [C]2, and [F]4), and to examine their specific bindings with metabotropic glutamate receptor subtype 2 (mGluR2) in rat brain sections by using in vitro autoradiography. These compounds were found to possess potent in vitro binding affinities (K: 8.0-34.1nM) for mGluR2 in rat brain homogenate. [C]1, [C]2, and [F]4 were synthesized by [C/F]alkylation of the corresponding phenol precursors with [C]methyl iodide or [F]fluoroethyl bromide with >98% radiochemical purity and 80-130GBq/μmol specific activity at the end of synthesis. In vitro autoradiography indicated that these radiotracers showed heterogeneous specific bindings in mGluR2-rich brain regions, such as the cerebral cortex, striatum, hippocampus, and granular layer of the cerebellum.