Radiosynthesis and preclinical evaluation of a carbon-11 labeled PET ligand for imaging metabotropic glutamate receptor 7.

Abstract

Metabotropic glutamate receptor 7 (mGlu₇) is a G protein-coupled receptor that is preferentially found in the active zone of neurotransmitter release in the central nervous system (CNS). mGlu₇ plays a vital role in memory, learning, and neuronal development, rendering it a potential target for treating epilepsy, depression, and anxiety. The development of noninvasive imaging ligands targeting mGlu₇ could help elucidate the functional significance of mGlu₇ and accelerate drug discovery for neurological and psychiatric disorders. In this report, a novel carbon-11 labeled positron emission tomography (PET) tracer designated [¹¹C]18 (codenamed MG7-2109) was synthesized via ¹¹C-methylation in 23% decay-corrected radiochemical yield (RCY). In vitro serum stability, serum protein binding, in vitro autoradiography and ex vivo biodistribution studies of [¹¹C]18 were conducted. Preliminary PET imaging results revealed a homogeneous distribution of [¹¹C]18 and rapid clearance in rodent brains. This study provides valuable insights into the development of mGlu₇-targeted PET tracer based on an isoxazolo(5,4-c)pyridine scaffold.