F-18-Labeled indole-based analogs as highly selective radioligands for imaging sigma-2 receptors in the brain
F-18-Labeled indole-based analogs as highly selective radioligands for imaging sigma-2 receptors in the brain
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F-18 标记的吲哚类似物作为高选择性放射性配体，用于大脑中 sigma-2 受体的成像
DOI：
10.1016/j.bmc.2017.05.019
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发表时间：
2017
影响因子：
3.5
通讯作者：
Jia Hongmei
中科院分区：
文献类型：
--
作者：
Wang Liang;Ye Jiajun;He Yingfang;Deuther-Conrad Winnie;Zhang Jinming;Zhang Xiaojun;Cui Mengchao;Steinbach Joerg;Huang Yiyun;Brust Peter;Jia Hongmei
我们设计合成了一系列以5，6-二甲氧基异吲哚啉或6，7-二甲氧基-1，2，3，4-四氢异喹啉为药效团的吲哚类σ 2受体配体，体外竞争结合实验表明，它们对σ 2受体都具有低纳摩尔亲和力（Ki= 1.79-5.23 nM）和高亚型选择性（Ki（σ2）/Ki（σ1）= 5,6 -708）。此外，它们对σ 2受体的选择性高于囊泡乙酰胆碱转运蛋白（>1000倍）。用自制的自动化合成装置，采用一锅两步反应法合成了相应的放射性示踪剂[18F] 16和[18F] 21，放化产率为10-15%，放化纯度> 99%。两种放射性示踪剂在小鼠体内均显示出较高的脑摄取和σ 2受体结合特异性。
We have designed and synthesized a series of indole-based σ2receptor ligands containing 5,6-dimethoxyisoindoline or 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline as pharmacophore.In vitrocompetition binding assays showed that all ten ligands possessed low nanomolar affinity (Ki= 1.79–5.23 nM) for σ2receptors and high subtype selectivity (Ki(σ2)/Ki(σ1) = 56–708). Moreover, they showed high selectivity for σ2receptor over the vesicular acetylcholine transporter (>1000-fold). The corresponding radiotracers [18F]16and [18F]21were prepared by an efficient one-pot, two-step reaction sequence with a home-made automated synthesis module, with 10–15% radiochemical yield and radiochemical purity of >99%. Both radiotracers showed high brain uptake and σ2receptor binding specificity in mice.