乙酰胆碱酯酶的体内成像是否需要亚纳摩尔级的结合亲和力？对18F标记的G379的研究。

Is subnanomolar binding affinity required for the in vivo imaging of acetylcholinesterase? Studies on 18F-labeled G379.

作者信息

Lee Sang-Yoon, Choe Yearn Seong, Ryu Eun Kyoung, Iimura Yoichi, Choi Yong, Lee Kyung-Han, Kim Byung-Tae

机构信息

Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

出版信息

Nucl Med Biol. 2006 Jan;33(1):91-4. doi: 10.1016/j.nucmedbio.2005.10.003.

DOI:10.1016/j.nucmedbio.2005.10.003

PMID:16459263

Abstract

Acetylcholinesterase (AChE) is an important cholinergic marker of Alzheimer's disease (AD) and shows reduced activity in postmortem AD brain tissues. 1-(4-Fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-fluoro-2-yl)methyl]piperidine (G379, ), an AChE inhibitor with a subnanomolar IC(50) (0.56 nM), was prepared as a (18)F-labeled radioligand ([(18)F]) and evaluated in mice. Metabolism studies of [(18)F] showed no metabolites in the mouse brain. Tissue distribution studies demonstrated its uniform regional distribution in the mouse brain, suggesting that this radioligand is not suitable for the in vivo imaging of AChE. This result along with reports on radiolabeled N-benzylpiperidine lactam benzisoxazole (IC(50) < 1 nM) and other radiolabeled benzylpiperidine derivatives (IC(50) > 1 nM) suggested that a subnanomolar IC(50) may not be the only important factor in determining the suitability of a radioligand for in vivo studies of AChE.

摘要

乙酰胆碱酯酶（AChE）是阿尔茨海默病（AD）的一种重要胆碱能标志物，在AD患者死后的脑组织中活性降低。1-（4-氟苄基）-4- [（5,6-二甲氧基-1-氧代茚满-2-氟-2-基）甲基]哌啶（G379），一种IC（50）为亚纳摩尔级（0.56 nM）的AChE抑制剂，被制备成一种（18）F标记的放射性配体（[（18）F]）并在小鼠体内进行评估。[（18）F]的代谢研究表明在小鼠脑中没有代谢产物。组织分布研究表明其在小鼠脑中区域分布均匀，这表明这种放射性配体不适用于AChE的体内成像。这一结果与关于放射性标记的N-苄基哌啶内酰胺苯并异恶唑（IC（50）<1 nM）和其他放射性标记的苄基哌啶衍生物（IC（50）> 1 nM）的报道表明，亚纳摩尔级的IC（50）可能不是决定放射性配体是否适用于AChE体内研究的唯一重要因素。