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5-(5-(6-[(11)C]甲基-3,6-二氮杂双环[3.2.0]庚烷-3-基)吡啶-2-基)-1H-吲哚作为一种潜在的用于在小鼠中成像脑 α7-nAChR 的 PET 放射性配体。

5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice.

机构信息

Division of Nuclear Medicine, Department of Radiology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA.

出版信息

Bioorg Med Chem. 2012 Jun 15;20(12):3698-702. doi: 10.1016/j.bmc.2012.04.056. Epub 2012 May 4.

DOI:10.1016/j.bmc.2012.04.056
PMID:22608919
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3527104/
Abstract

The radiosynthesis and in vivo evaluation of 5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [(11)C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-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 [(11)C]CH(3)I afforded [(11)C]rac-1 in an average radiochemical yield of 30 ± 5% (n=5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n=5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [(11)C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.

摘要

5-(5-(6-[(11)C]甲基-3,6-二氮杂双环[3.2.0]庚烷-3-基)吡啶-2-基)-1H-吲哚 [(11)C]rac-(1) 的放射性合成和体内评价，一种潜在的用于 α7 烟碱型乙酰胆碱受体 (α7-nAChR) 的 PET 示踪剂，被描述。非放射性标准 rac-1 和相应的去甲基前体 7 的合成通过几个反应步骤实现。7 与 [(11)C]CH(3)I 的放射性甲基化以 30 ± 5%（n=5）的平均放射化学产率得到 [(11)C]rac-1，具有高放射化学纯度和 444 ± 74 GBq/μmol（n=5）的平均比放射性。从结束轰炸到总合成时间为 30 分钟。在小鼠中的生物分布研究表明，[(11)C]rac-1 穿透血脑屏障并特异性标记神经元 α7-nAChR。

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