Imaging the trace amine-associated receptor 1 by positron emission tomography
Imaging the trace amine-associated receptor 1 by positron emission tomography
复制标题
通过正电子发射断层扫描对痕量胺相关受体 1 进行成像
DOI：
10.1016/j.tetlet.2021.153007
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发表时间：
2021-04-16
影响因子：
1.8
通讯作者：
Liang, Steven H.
中科院分区：
文献类型：
--
作者：
Sun, Jiyun;Chen, Jiahui;Liang, Steven H.
微量胺相关受体1（TAAR 1）与药物成瘾、精神分裂症、抑郁症和帕金森病（PD）有关。迄今为止，还没有关于TAAR 1靶向探针用于体内受体密度的非侵入性定量的报道。在此，我们报告了C-11标记的TAAR 1高亲和力拮抗剂N-（3-甲氧基苯基）-6-（吡咯烷-1-基）-5-（三氟甲基）烟酰胺[C-11]4（也称为[C-11] TAAR 1 -1911）的合成，以及其用于正电子发射断层扫描（PET）成像的物理化学和临床前评估。使用[C-11] CH 3 I和碱NaOH以良好的放射化学产率（相对于起始[C-11]CO2，非衰变校正的14%）、优异的放射化学纯度（>99%）和高摩尔活性（>37 GBq/mmol）提供该PET配体。尽管有良好的体外性能特征，[C-11]4未表现出体内特异性，可能是由于快速代谢降解。进一步的研究是必要的，以确定一个合适的TAAR 1 PET示踪剂，这将最终有助于开发TAAR 1导向的治疗药物。(C)2021爱思唯尔有限公司保留所有权利。
Trace amine-associated receptor 1 (TAAR1) has been implicated in drug addiction, schizophrenia, depression and Parkinson's disease (PD). To date, there are no reports on TAAR1-targeted probes for non-invasive quantification of receptor density in vivo. Herein, we report the synthesis of a C-11-labeled TAAR1 high-affinity antagonist N-(3-methoxyphenyl)-6-(pyrrolidin-1-yl)-5-(trifluoromethyl)nicotinamide [C-11]4 (also named [C-11]TAAR1-1911), as well as its physicochemical and preclinical evaluations for positron emission tomography (PET) imaging. This PET ligand was afforded using [C-11]CH3I with the base NaOH in good radiochemical yield (non-decay corrected 14% relative to starting [C-11]CO2), excellent radiochemical purities (>99%) and high molar activities (>37 GBq/mmol). Despite promising in vitro performance characteristics, [C-11]4 did not exhibit in vivo specificity, potentially owing to fast metabolic degradation. Further studies are warranted to identify a suitable TAAR1 PET tracer, which would ultimately aid the development of TAAR1-directed therapeutic agents. (C) 2021 Elsevier Ltd. All rights reserved.