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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Prabhakaran, Jaya¹  Majo, Vattoly J.¹  Milak, Matthew S.^1,3  Kassir, Suham A.³  Palner, Mikael¹  Savenkova, Lyudmila¹  Mali, Pratap³  Arango, Victoria^1,3  Mann, J. John^1,2,3  Parsey, Ramin V.^1,3  Kumar, J. S. Dileep^1,2,3 

[1] Columbia Univ, Dept Psychiat, Div Mol Imaging & Neuropathol, New York, NY 10032 USA

[2] Columbia Univ, Dept Radiol, New York, NY 10032 USA

[3] New York State Psychiat Inst & Hosp, New York, NY 10032 USA

关键词: mGluR1 receptors;    Autoradiography;    Positron emission tomography;    Biological imaging;    Human postmortem;   

DOI  :  10.1016/j.bmcl.2010.04.146

来源: Elsevier

【 摘 要 】

Synthesis, in vitro and in vivo evaluation of [O-methyl-C-11]dimethylamino-3(4-methoxyphenyl)-3H-pyrido[ 30',20': 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 [C-11]MeOTf in presence of NaOH afforded [C-11]1 in 30% yield (EOS) with >99% chemical and radiochemical purities and with a specific activity of 3-5 Ci/mu mol (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 [C-11]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. (C) 2010 Elsevier Ltd. All rights reserved.

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