Synthesis, in vitro and in vivo evaluation of [¹¹C]MMTP: A potential PET ligand for mGluR1 receptors

Synthesis, in vitro and in vivo evaluation of [O-methyl- ¹¹C]dimethylamino-3(4-methoxyphenyl)-3H-pyrido[3′,2′:4,5] thieno[3,2-d]pyrimidin-4-one (1), a potential imaging agent for mGluR1 receptors using PET are described. Synthesis of the corresponding desmethyl precursor 2 was achieved by demethylation of the methoxyphenyl compound 1 in 90% yield. Methylation using [¹¹C]MeOTf in presence of NaOH afforded [ ¹¹C]1 in 30% yield (EOS) with >99% chemical and radiochemical purities and with a specific activity of 3-5 Ci/μmol (n = 6). The total synthesis time was 30 min from EOB. The radiotracer selectively labeled mGluR1 receptors in slide-mounted sections of postmortem human brain containing cerebellum, hippocampus, prefrontal cortex and striatum as demonstrated by in vitro autoradiography using phosphor-imaging. PET studies in anesthetized baboon show that [¹¹C]1 penetrates the BBB and accumulates in cerebellum, a region reported to have higher expression of mGluR1. These findings suggest [¹¹C]1 is a promising PET radiotracer candidate for mGluR1.