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Development of TASP0410457 (TASP457), a novel dihydroquinolinone derivative as a PET radioligand for central histamine H3 receptors
https://repo.qst.go.jp/records/47652
https://repo.qst.go.jp/records/476524c1f00ab-357c-4bfa-9c77-883217cd90eb
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-03-08 | |||||
| タイトル | ||||||
| タイトル | Development of TASP0410457 (TASP457), a novel dihydroquinolinone derivative as a PET radioligand for central histamine H3 receptors | |||||
| 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 |
Koga, Kazumi
× Koga, Kazumi× Maeda, Jun× Tokunaga, Masaki× Hanyu, Masayuki× Kawamura, Kazunori× Ohmichi, Mari× Nakamura, Toshio× Nagai, Yuji× Seki, Chie× Kimura, Yasuyuki× Minamimoto, Takafumi× Zhang, Ming-Rong× Fukumura, Toshimitsu× Suhara, Tetsuya× Higuchi, Makoto× 古閑 一実× 前田 純× 徳永 正希× 破入 正行× 河村 和紀× 永井 裕司× 関 千江× 木村 泰之× 南本 敬史× 張 明栄× 福村 利光× 須原 哲也× 樋口 真人 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background: Histamine H3 receptor (H3R) is a potential therapeutic target of sleep- and cognition-related disorders. The purpose of the present study is to develop a novel positron emission tomography (PET) ligand for H3Rs from dihydroquinolinone derivatives, which we previously found to have high affinity with these receptors. Methods: Six compounds were selected from a dihydroquinolinone compound library based on structural capability for 11C labeling and binding affinity for H3Rs. Their in-vivo kinetics in the rat brain were examined in a comparative manner by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Chemicals with appropriate kinetic properties were then labeled with 11C and evaluated in rats and monkeys using PET. Results: Of the six compounds, TASP0410457 (also diminutively called TASP457) and TASP0434988 exhibited fast kinetics and relatively high brain uptakes in ex vivo LC-MS/MS, and were selected as candidate PET imaging agents. PET data in rat brains were mostly consistent with LC-MS/MS findings, and rat and monkey PET scans demonstrated that [11C]TASP0410457 was superior to [11C]TASP0434988 for high-contrast H3R PET imaging. In the monkey brain PET, distribution volume for [11C]TASP0410457 could be quantified, and receptor occupancy by nonradioactive compounds was measurable using this radioligand. The specific binding of [11C]TASP0410457 to H3Rs was confirmed by autoradiography using rat and monkey brain sections. Conclusions: We developed [11C]TASP0410457 as a radioligand enabling a robust quantification of H3Rs in all brain regions, and demonstrated the utility of ex vivo LC-MS/MS and in vivo PET assays for selecting appropriate imaging tracers. [11C]TASP0410457 will help to examine the implication of H3Rs in neuropsychiatric disorders and to characterize emerging therapeutic agents targeting H3Rs. |
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| 書誌情報 |
EJNMMI Research 巻 6, 号 1, p. 11, 発行日 2016-02 |
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| 出版者 | ||||||
| 出版者 | Springer | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2191-219X | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 26860293 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1186/s13550-016-0170-2 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.ejnmmires.com/content/6/1/11 | |||||
| 関連名称 | http://www.ejnmmires.com/content/6/1/11 | |||||
