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Difference in brain distribustions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel
https://repo.qst.go.jp/records/45201
https://repo.qst.go.jp/records/452015da55277-7ba1-4d9b-bac0-e77c0222c2a5
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-06-17 | |||||
| タイトル | ||||||
| タイトル | Difference in brain distribustions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Fuchigami, Takeshi
× Fuchigami, Takeshi× Haradahira, Terushi× Fujimoto, Noriko× Okauchi, Takashi× Maeda, Jun× Suzuki, Kazutoshi× Suhara, Tetsuya× Yamamoto, Fumihiko× Mukai, Takahiro× Magata, Yasuhiro× Maeda, Minoru× et.al× 淵上 剛志× 原田平 輝志× 岡内 隆× 前田 純× 鈴木 和年× 須原 哲也× 前田 稔 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | High-affinity iodine- and ethyl-C-5 substituted analogs of 4-hydroxy-3-(3-[11C]methoxyphenyl)-2(1H)-quinolone ([11C]4HQ) were synthesized as new positron emission tomography radioligands for the glycine-binding sites of the N-methyl-d-aspartate (NMDA) ion channel. Although both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[11C]4HQ (5Et-[11C]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site agonists and antagonists. In contrast, 5-iodo-[11C]4HQ (5I-[11C]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[11C]4HQ and 5I-[11C]4HQ was quite similar to that previously observed between [11C]L-703,717 and [11C]4HQ, both glycine-site antagonists. In vivo brain uptakes of these 11C-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes of 5Et- and 5I-[11C]4HQ at 1 min after intravenous injections were comparable to that of [11C]4HQ, but they were 1.3-2.1 times higher than that of [11C]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [11C]4HQ and 5Et-[11C]4HQ in contrast to [11C]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[11C]4HQ (16-36% inhibition) but not that of 5I-[11C]4HQ. In this study, it was found that a small structural change in [11C]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding sites for [11C]4-hydroxyquinolones on the NMDA ion channel - agonist-sensitive and agonist-insensitive (or antagonist-preferring) sites. | |||||
| 書誌情報 |
Nuclear Medicine and Biology 巻 35, 号 2, p. 203-212, 発行日 2008-02 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0969-8051 | |||||
