近日,日本横滨市立大学Takuya Takahashi及其团队利用正电子发射断层显像在活人脑中实现AMPA受体可视化。这一研究成果2020年1月20日在线发表于国际学术期刊《自然—医学》。
Title: Visualization of AMPA receptors in living human brain with positron emission tomography
Author: Tomoyuki Miyazaki, Waki Nakajima, Mai Hatano, Yusuke Shibata, Yoko Kuroki, Tetsu Arisawa, Asami Serizawa, Akane Sano, Sayaka Kogami, Tomomi Yamanoue, Kimito Kimura, Yushi Hirata, Yuuki Takada, Yoshinobu Ishiwata, Masaki Sonoda, Masaki Tokunaga, Chie Seki, Yuji Nagai, Takafumi Minamimoto, Kazunori Kawamura, Ming-Rong Zhang, Naoki Ikegaya, Masaki Iwasaki, Naoto Kunii, Yuichi Kimura, Fumio Yamashita, Masataka Taguri, Hideaki Tani, Nobuhiro Nagai, Teruki Koizumi, Shinichiro Nakajima, Masaru Mimura, Michisuke Yuzaki, Hiroki Kato, Makoto Higuchi, Hiroyuki Uchida, Takuya Takahashi
Issue&Volume: 2020-01-20
Abstract: Although aberrations in the number and function of glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are thought to underlie neuropsychiatric disorders, no methods are currently available for visualizing AMPA receptors in the living human brain. Here we developed a positron emission tomography (PET) tracer for AMPA receptors. A derivative of 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide radiolabeled with 11C ([11C]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [11C]K-2 in the brain according to Logan graphical analysis (UMIN000020975; study design: non-randomized, single arm; primary outcome: dynamics and distribution volumes of [11C]K-2 in the brain; secondary outcome: adverse events of [11C]K-2 during the 4–10d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [11C]K-2 uptake in the epileptogenic focus of patients with mesial temporal lobe epilepsy, which was closely correlated with the local AMPA receptor protein distribution in surgical specimens from the same individuals (UMIN000025090; study design: non-randomized, single arm; primary outcome: correlation between [11C]K-2 uptake measured with PET before surgery and AMPA receptor protein density examined by biochemical study after surgery; secondary outcome: adverse events during the 7d following PET scan; this trial met prespecified endpoints). Thus, [11C]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders.
DOI: 10.1038/s41591-019-0723-9
Source: https://www.nature.com/articles/s41591-019-0723-9
Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex