Synthesis, in vitro and in vivo evaluation of [11C]MMTP: A potential PET ligand for mGluR1 receptors
2010; Elsevier BV; Volume: 20; Issue: 12 Linguagem: Inglês
10.1016/j.bmcl.2010.04.146
ISSN1464-3405
AutoresJaya Prabhakaran, Vattoly J. Majo, Matthew S. Milak, Suham Kassir, Mikael Palner, Lyudmila Savenkova, Mali Pratap, Victoria Arango, J. John Mann, Ramin V. Parsey, J.S. Dileep Kumar,
Tópico(s)Pharmacological Receptor Mechanisms and Effects
ResumoSynthesis, 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.
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