論文

査読有り
2020年2月

Visualization of AMPA receptors in living human brain with positron emission tomography

NATURE MEDICINE
  • 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

26
2
開始ページ
281
終了ページ
+
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41591-019-0723-9
出版者・発行元
NATURE PUBLISHING GROUP

Although aberrations in the number and function of glutamate AMPA (alpha-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 C-11 ([C-11]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [C-11]K-2 in the brain according to Logan graphical analysis (; study design: non-randomized, single arm; primary outcome: dynamics and distribution volumes of [C-11]K-2 in the brain; secondary outcome: adverse events of [C-11]K-2 during the 4-10 d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [C-11]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 (; study design: non-randomized, single arm; primary outcome: correlation between [C-11]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 7 d following PET scan; this trial met prespecified endpoints). Thus, [C-11]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders.

Web of Science ® 被引用回数 : 14

リンク情報
DOI
https://doi.org/10.1038/s41591-019-0723-9
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000510551600001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/s41591-019-0723-9
  • ISSN : 1078-8956
  • eISSN : 1546-170X
  • Web of Science ID : WOS:000510551600001

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