WEKO3
アイテム
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Development of 1-N-(11)C-Methyl-l- and -d-Tryptophan for pharmacokinetic imaging of the immune checkpoint inhibitor 1-Methyl-Tryptophan.
https://repo.qst.go.jp/records/47380
https://repo.qst.go.jp/records/47380a7729bc2-168e-452a-9042-6339ab313f73
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2016-01-18 | |||||
タイトル | ||||||
タイトル | Development of 1-N-(11)C-Methyl-l- and -d-Tryptophan for pharmacokinetic imaging of the immune checkpoint inhibitor 1-Methyl-Tryptophan. | |||||
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 |
Xie, Lin
× Xie, Lin× Maeda, Jun× Kumata, Katsushi× Yui, Joji× Zhang, Yiding× Hatori, Akiko× Nengaki, Nobuki× Wakizaka, Hidekatsu× Fujinaga, Masayuki× Yamasaki, Tomoteru× Shimoda, Yoko× Higuchi, Makoto× Suhara, Tetsuya× Wang, Feng× Zhang, Ming-Rong× 謝 琳× 前田 純× 熊田 勝志× 由井 譲二× 張 一鼎× 羽鳥 晶子× 念垣 信樹× 脇坂 秀克× 藤永 雅之× 山崎 友照× 下田 陽子× 樋口 真人× 須原 哲也× 張 明栄 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 1-Methyl-tryptophan (1MTrp) is known as a specific inhibitor targeting the immune- checkpoint protein indoleamine-2,3-dioxygenase, in two stereoisomers of levorotary (l) and dextrorotary (d). A long-standing debate exists in immunology and oncology: which stereoisomer has the potential of antitumor immunotherapy. Herein, we developed two novel radioprobes, 1-N-(11)C-methyl-l- and -d-tryptophan ((11)C-l-1MTrp and (11)C-d-1MTrp), without modifying the chemical structures of the two isomers, and investigated their utility for pharmacokinetic imaging of the whole body. (11)C-l-1MTrp and (11)C-d-1MTrp were synthesized rapidly with radiochemical yields of 47 ± 6.3% (decay-corrected, based on (11)C-CO2), a radiochemical purity of >98%, specific activity of 47-130 GBq/μmol, and high enantiomeric purity. PET/CT imaging in rats revealed that for (11)C-l-1MTrp, the highest distribution of radioactivity was observed in the pancreas, while for (11)C-D-1MTrp, it was observed in the kidney. Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. Both (11)C-l-1MTrp and (11)C-d-1MTrp are therefore useful PET probes for delineating the distribution and action of the checkpoint inhibitor 1MTrp in vivo. This study represents the first step toward using whole-body and real-time insight to disentangle the antitumor potential of the two stereoisomers of 1MTrp, and it can facilitate the development of 1MTrp immunotherapy. | |||||
書誌情報 |
Scientific Reports (Online Only URL:http://www.nature.com/srep/index.html) 巻 5, p. 16417, 発行日 2015-11 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2045-2322 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 26552594 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | doi:10.1038/srep16417 |