5-(5-(6-[up>11up>C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole as a potential PET radioligand for imaging cerebral 伪7-nAChR in mice

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• 作者：Yongjun Gaoup> ; up>up>ygao5@jhmi.eduup> ; Hayden T. Ravert ; Heather Valentine ; Ursula Scheffel ; Paige Finley ; Dean F. Wong ; Robert F. Dannals ; Andrew G. Horti
• 关键词：Positron emission tomography ; Radioligand ; Nicotinic acetylcholine receptors ; 伪7-nAChR
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 June, 2012
• 卷：20
• 期：12
• 页码：3698-3702
• 文件大小：386 K

摘要

The radiosynthesis and in vivo evaluation of 5-(5-(6-[up>11up>C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [up>11up>C]rac-(1), a potential PET tracer for 伪7 nicotinic acetylcholine receptors (伪7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [up>11up>C]CH₃I afforded [up>11up>C]rac-1 in an average radiochemical yield of 30 卤 5%(n = 5) with high radiochemical purity and an average specific radioactivity of 444 卤 74 GBq/渭mol (n = 5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [up>11up>C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal 伪7-nAChRs.