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

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 11 C-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.