Synthesis and Characterization of 5-(2-Fluoro-4-[¹¹C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2.

ABSTRACT: Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for several neuropsychiatric disorders. An mGluR2 function in etiology could be unveiled by positron emission tomography (PET). In this regard, 5-(2-fluoro-4-[¹¹C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide ([¹¹C]13, [¹¹C]mG2N001), a potent negative allosteric modulator (NAM), was developed to support this endeavor. [¹¹C]13 was synthesized via the O-[¹¹C]methylation of phenol 24 with a high molar activity of 212 ± 76 GBq/μmol (n = 5) and excellent radiochemical purity (>99%). PET imaging of [¹¹C]13 in rats demonstrated its superior brain heterogeneity and reduced accumulation with pretreatment of mGluR2 NAMs, VU6001966 (9) and MNI-137 (26), the extent of which revealed a time-dependent drug effect of the blocking agents. In a nonhuman primate, [¹¹C]13 selectively accumulated in mGluR2-rich regions and resulted in high-contrast brain images. Therefore, [¹¹C]13 is a potential candidate for translational PET imaging of the mGluR2 function.

SUBMITTER: Yuan G 

PROVIDER: S-EPMC9434702 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature