Imaging of Transmembrane AMPA Receptor Regulatory Proteins by Positron Emission Tomography.
Imaging of Transmembrane AMPA Receptor Regulatory Proteins by Positron Emission Tomography.
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DOI：
10.1021/acs.jmedchem.2c00377
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发表时间：
2022-07-14
影响因子：
7.3
通讯作者：
Liang, Steven
中科院分区：
文献类型：
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作者：
Yu, Qingzhen;Kumata, Katsushi;Rong, Jian;Chen, Zhen;Yamasaki, Tomoteru;Chen, Jiahui;Xiao, Zhiwei;Ishii, Hideki;Hiraishi, Atsuto;Shao, Tuo;Zhang, Yiding;Hu, Kuan;Xie, Lin;Fujinaga, Masayuki;Zhao, Chunyu;Mori, Wakana;Collier, Thomas;Haider, Ahmed;Tomita, Susumu;Zhang, Ming-Rong;Liang, Steven
跨膜α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）受体调节蛋白γ - 8（TARP γ - 8）是AMPA受体的一个辅助亚基，介导包括学习和记忆在内的多种脑功能。TARP γ - 8已成为治疗中枢神经系统疾病颇具潜力的靶点。尽管已付出诸多努力，但先前报道的TARP γ - 8正电子发射断层扫描（PET）放射性配体，如[11C]TARP - 1903或[11C]TARP - 1811系列，存在脑摄取有限和/或体内非特异性结合高的问题。在此，我们研发了两种新型的11C标记探针，[11C]8和[11C]15（也称为[11C]TARP - 2105），其中后者在体外和体内均显示出合理的脑摄取以及对TARP γ - 8的特异性结合。通过使用市售的TARP γ - 8抑制剂JNJ - 55511118进行阻断实验，富含TARP γ - 8的海马体证实了这一点。总体而言，[11C]15展现出有前景的示踪剂特性，证明其是一种先导性PET配体，可用于对哺乳动物大脑中的TARP γ - 8进行无创定量分析。
The transmembrane α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptor regulatory protein γ−8 (TARP γ−8) constitutes an auxiliary subunit of AMPA receptors, which mediates various brain functions including learning and memory. TARP γ−8 has emerged as a promising therapeutic target for central nervous system disorders. Despite considerable efforts, previously reported TARP γ−8 PET radioligands, such as [11C]TARP-1903 or the [11C]TARP-1811 series, were plagued by limited brain uptake and/or high nonspecific binding in vivo. Herein, we developed two novel 11C-labeled probes, [11C]8 and [11C]15 (also named as [11C]TARP-2105), of which the latter exhibited reasonable brain uptake as well as specific binding towards TARP γ−8 both in vitro and in vivo, as confirmed for the TARP γ−8-rich hippocampus by blocking experiments with the commercially available TARP γ−8 inhibitor, JNJ-55511118. Overall, [11C]15 exhibited promising tracer characteristics and proved to be a lead positron-emission tomography (PET) ligand for non-invasive quantification of TARP γ−8 in the mammalian brain.
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影响因子：
3.7
作者：
Azumaya, Caleigh M.;Days, Emily L.;Nakagawa, Terunaga
通讯作者：
Nakagawa, Terunaga
影响因子：
5.6
作者：
French, Jacqueline A.;Krauss, Gregory L.;Laurenza, Antonio
通讯作者：
Laurenza, Antonio
影响因子：
16.2
作者：
Jackson AC;Nicoll RA
通讯作者：
Nicoll RA
影响因子：
16.2
作者：
Kessels, Helmut W.;Malinow, Roberto
通讯作者：
Malinow, Roberto
DOI：
10.1002/anie.201805501
发表时间：
2019-02-25
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Deng X;Rong J;Wang L;Vasdev N;Zhang L;Josephson L;Liang SH
通讯作者：
Liang SH