18F-ASEM，一种放射性标记的 α7-烟碱型乙酰胆碱受体显像剂，用于正电子发射断层扫描（PET）。
18F-ASEM, a radiolabeled antagonist for imaging the α7-nicotinic acetylcholine receptor with PET.
机构信息
Department of Radiology, Johns Hopkins School of Medicine, Baltimore, Maryland.
出版信息
J Nucl Med. 2014 Apr;55(4):672-7. doi: 10.2967/jnumed.113.132068. Epub 2014 Feb 20.
UNLABELLED
The α7-nicotinic cholinergic receptor (α7-nAChR) is a key mediator of brain communication and has been implicated in a wide variety of central nervous system disorders. None of the currently available PET radioligands for α7-nAChR are suitable for quantitative PET imaging, mostly because of insufficient specific binding. The goal of this study was to evaluate the potential of (18)F-ASEM ((18)F-JHU82132) as an α7-nAChR radioligand for PET.
METHODS
The inhibition binding assay and receptor functional properties of ASEM were assessed in vitro. The brain regional distribution of (18)F-ASEM in baseline and blockade were evaluated in DISC1 mice (dissection) and baboons (PET).
RESULTS
ASEM is an antagonist for the α7-nAChR with high binding affinity (Ki = 0.3 nM). (18)F-ASEM readily entered the baboon brain and specifically labeled α7-nAChR. The in vivo specific binding of (18)F-ASEM in the brain regions enriched with α7-nAChRs was 80%-90%. SSR180711, an α7-nAChR-selective partial agonist, blocked (18)F-ASEM binding in the baboon brain in a dose-dependent manner, suggesting that the binding of (18)F-ASEM was mediated by α7-nAChRs and the radioligand was suitable for drug evaluation studies. In the baboon baseline studies, the brain regional volume of distribution (VT) values for (18)F-ASEM were 23 (thalamus), 22 (insula), 18 (hippocampus), and 14 (cerebellum), whereas in the binding selectivity (blockade) scan, all regional VT values were reduced to less than 4. The range of regional binding potential values in the baboon brain was from 3.9 to 6.6. In vivo cerebral binding of (18)F-ASEM and α7-nAChR expression in mutant DISC1 mice, a rodent model of schizophrenia, was significantly lower than in control animals, which is in agreement with previous postmortem human data.
CONCLUSION
(18)F-ASEM holds promise as a radiotracer with suitable imaging properties for quantification of α7-nAChR in the human brain.
未加标注
α7-烟碱型乙酰胆碱受体（α7-nAChR）是大脑通讯的关键介质，与多种中枢神经系统疾病有关。目前尚无可用于定量 PET 成像的 α7-nAChR 的 PET 放射性配体，这主要是由于特异性结合不足。本研究的目的是评估（18）F-ASEM（（18）F-JHU82132）作为 PET 中 α7-nAChR 放射性配体的潜力。
方法
在体外评估 ASEM 的抑制结合测定和受体功能特性。在 DISC1 小鼠（解剖）和狒狒（PET）中评估（18）F-ASEM 在基线和阻断时的脑区分布。
结果
ASEM 是一种具有高结合亲和力（Ki=0.3 nM）的 α7-nAChR 拮抗剂。（18）F-ASEM 可轻易进入狒狒大脑，并特异性标记 α7-nAChR。富含 α7-nAChR 的脑区中（18）F-ASEM 的体内特异性结合率为 80%-90%。SSR180711，一种 α7-nAChR 选择性部分激动剂，可剂量依赖性地阻断狒狒脑内（18）F-ASEM 的结合，表明（18）F-ASEM 的结合由 α7-nAChR 介导，且放射性配体适合药物评估研究。在狒狒基线研究中，（18）F-ASEM 的脑区分布容积（VT）值分别为 23（丘脑）、22（岛叶）、18（海马）和 14（小脑），而在结合选择性（阻断）扫描中，所有脑区的 VT 值均降至 4 以下。狒狒脑内（18）F-ASEM 的区域结合潜能值范围为 3.9 至 6.6。在精神分裂症啮齿动物模型突变 DISC1 小鼠中，（18）F-ASEM 和 α7-nAChR 的脑内结合明显低于对照动物，这与先前的人体尸检数据一致。
结论
（18）F-ASEM 有望成为一种放射性示踪剂，具有适合人类大脑 α7-nAChR 定量成像的成像特性。
Zotero 插件