Synthesis and evaluation of 6-[11C]methoxy-3-[2-[l-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole as an in vivo radioligand for acetylcholinesterase
Synthesis and evaluation of 6-[11C]methoxy-3-[2-[l-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole as an in vivo radioligand for acetylcholinesterase
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DOI：
10.1016/s0969-8051(98)00078-x
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发表时间：
1999-01-01
影响因子：
3.1
通讯作者：
Kilbourn, MR
中科院分区：
文献类型：
--
作者：
Brown-Proctor, C;Snyder, SE;Kilbourn, MR
6-Methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1，2-benzisoxazole是一种高亲和力(K-I=8.2nM)的乙酰胆碱酯酶(AChE)可逆抑制剂。通过脱甲基前体与[C-11]三氟甲磺酸甲酯在N，N二甲基甲酰胺中的烷基化反应，制得了放化纯度高(~gt；97%)、比活度为37+/-20GBq/mMol的碳-11标记形式。在小鼠身上的活体研究显示，血脑通透性良好，但脑内区域分布基本均匀。因此，尽管在体外和体内具有AChE抑制剂的活性，但6-[C-11]methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1，2-benzisoxazole似乎不是在哺乳动物大脑中进行AChE体内成像研究的良好候选者。核医学生物26；1：99-103,1999。(C)1999年爱思唯尔科学公司。
6-Methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole is a high affinity (K-i = 8.2 nM) reversible inhibitor of acetylcholinesterase (AChE). The carbon-11 labeled form was prepared in high (>97%) radiochemical purity and with specific activities of 37 +/- 20 GBq/mu mol at end of synthesis, by the alkylation of the desmethyl precursor with [C-11]methyl trifluoromethanesulfonate in N,N dimethylformamide at room temperature. In vivo studies in mice demonstrated good blood brain permeability but essentially uniform regional brain distribution. Thus, despite in vitro and in vivo activity as an AChE inhibitor, 6-[C-11]methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole does not appear to be a good candidate for in vivo imaging studies of AChE in the mammalian brain. NUCL MED BIOL 26;1: 99-103, 1999. (C) 1999 Elsevier Science Inc.