Evaluation of the binding characteristics of [5-(11)C-methoxy]Donepezil in the rat brain for in vivo visualization of acetylcholinesterase.
Evaluation of the binding characteristics of [5-(11)C-methoxy]Donepezil in the rat brain for in vivo visualization of acetylcholinesterase.
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评估[5-(11)C-甲氧基]多奈哌齐在大鼠脑中的结合特征，以实现乙酰胆碱酯酶的体内可视化。
DOI：
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发表时间：
2003
影响因子：
3.5
通讯作者：
K. Yanai
中科院分区：
文献类型：
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作者：
Y. Funaki;Motohisa Kato;R. Iwata;E. Sakurai;E. Sakurai;M. Tashiro;T. Ido;K. Yanai
多奈哌齐是一种乙酰胆碱酯酶（AChE）抑制剂，尽管其对AChE的抑制作用已被研究，但尚未用放射性示踪剂评估其结合特性。本研究的目的是研究乙酰胆碱酯是否可以用多奈哌齐在体内和体外可视化。[5-(11)C-甲氧基]多奈哌齐以[(11)C]三氟化甲酯为原料，经o -甲基化合成。[(11)C]多奈哌齐与脑匀浆的结合在脑干和纹状体中较高，在小脑中最低。体外放射自显影研究成功证明了[(11)C]多奈哌齐与大鼠脑内乙酰胆碱酯的特异性结合。结合的IC（50）值约为10 nM，与报道的抑制酶活性的IC（50）值（6 nM）相当。饱和实验表明，[(11)C]多奈哌齐体外结合的B（max）和K(d)分别为65 fmol/mg组织和39.8 nM。根据体外结合，[(11)C]多奈哌齐在大鼠脑内的体内分布具有异质性。在阻断实验中，由于存在大量未标记的多奈哌齐，异质分布消失。这些数据表明，[5-(11)c -甲氧基]多奈哌齐可能有助于通过正电子发射断层扫描对人脑中的乙酰胆碱酯进行无创成像。
Donepezil, an acetylcholinesterase (AChE) inhibitor, has not been evaluated for its binding characteristics using a radioactive tracer, although its inhibitory action on AChE has been studied. The aim of this research is to examine whether AChE can be visualized in vivo and in vitro with [(11)C]donepezil. [5-(11)C-methoxy]Donepezil was synthesized by O-methylation using [(11)C]methyl triflate. The binding of [(11)C]donepezil to brain homogenates was higher in the brain stem and striatum, and it was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [(11)C]donepezil to AChE in the rat brain. The IC(50) value of binding was approximately 10 nM, which is comparable to the reported value for inhibiting enzyme activity (6 nM). Saturation experiments revealed that the B(max) and K(d) of [(11)C]donepezil binding in vitro are 65 fmol/mg tissue and 39.8 nM, respectively. In accordance with the in vitro bindings, the in vivo distribution of [(11)C]donepezil was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of a large amount of unlabeled donepezil. These data suggest that [5-(11)C-methoxy]donepezil can be potentially useful to image AChE non-invasively in the human brain by positron emission tomography.
DOI：
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发表时间：
1996-07
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
N. Volkow;J. Fowler;S. Gatley;J. Logan;G. Wang;Yu-Shin Ding;S. Dewey
通讯作者：
N. Volkow;J. Fowler;S. Gatley;J. Logan;G. Wang;Yu-Shin Ding;S. Dewey