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Radiosynthesis and pharmacokinetic comparison of 1-N-[11C]methyl]-L- and -D-tryptophan
https://repo.qst.go.jp/records/71732
https://repo.qst.go.jp/records/71732b4fc7742-cbae-4426-9c41-e2f5275e113a
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-06-18 | |||||
| タイトル | ||||||
| タイトル | Radiosynthesis and pharmacokinetic comparison of 1-N-[11C]methyl]-L- and -D-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_c94f | |||||
| 資源タイプ | conference object | |||||
| 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 |
Kumata, Katsushi
× Kumata, Katsushi× Xie, Lin× Yui, Joji× Hatori, Akiko× Zhang, Yiding× Nengaki, Nobuki× Fujinaga, Masayuki× Yamasaki, Tomoteru× Shimoda, Yoko× Maeda, Jun× Zhang, Ming-Rong× 熊田 勝志× 謝 琳× 由井 譲二× 羽鳥 晶子× 張 一鼎× 念垣 信樹× 藤永 雅之× 山崎 友照× 下田 陽子× 前田 純× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: The indole-containing small molecule 1-methyl-tryptophan (1MTrp) is known as a specific inhibitor targeted immune checkpoint protein indoleamine-2,3-dioxygenase (IDO)- switching off the effector T cells of the immune system to support tumor growth. 1MTrp has shown attractive antitumor activity without noticeable toxicity [1], and its phase I trial had been completed in 2014. However, 1MTrp exists as 2 stereoisomers of L and D. Most preclinical studies have employed the racemic mixture, thus leaving a long-standing debate in immunology and oncology, which stereoisomers have the potential of immune checkpoint inhibitor [2,3]. To remove the blindfold of 1MTrp effects and guide its immunotherapy development, we synthesized 1-N-[11C]methyl]-L- and -D-tryptophan ([11C]L-1MTrp and [11C]D-1-MTrp) and compared their pharmacokinetics by PET. Methods: [11C]L-1MTrp and [11C]D-1MTrp were synthesized by reaction of the corresponding Boc-Trp-OEt with [11C]CH3I at 80 °C for 5 min, followed by deprotection with 2 N HCl at 100 °C for 5 min. Pharmacokinetics of the L and D isomers were compared by dynamic PET scans and biodistribution study following the injection of the radioprobes in rats. Results: [11C]L-1MTrp and [11C]D-1MTrp were obtained with radiochemical yields of 47.0 ± 6.3% (n = 80, based on [11C]CO2, EOS), radiochemical purity of > 98%, and specific activity of 47―130 GBq/μmol, showing high enantiomeric purity. PET imaging in rats revealed [11C]L-1MTrp had the highest accumulation of radioactivity (SUV 2.88 ± 0.03) in the pancreas with high IDO expression, while [11C]D-1MTrp showed the highest uptake (SUV 1.16 ± 0.03) in the kidney at 60 min after the radioprobes injection respectively. Ex vivo biodistribution results supported the PET images and indicated that uptake of L isomer in each organ was significantly higher than D isomer except in the kidney. Quite different tissue distribution was verified between the 2 stereoisomers. Conclusions: Both [11C]L-1MTrp and [11C]D-1MTrp are useful PET probes for tracking the pharmacokinetics of 1MT in vivo. Imaging the immune checkpoint inhibitors would enable us to take a new look at cancer immunotherapy and drug development. \nReference: [1].Muller AJ, et al. Nat Med. 2005;11:312. [2]. Hou DY, et al. Cancer Res. 2007;67:792. [3] Lob S, et al. Blood. 2008;111:2152. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 21st International Symposium on Radiopharmaceutical Sciences | |||||
| 発表年月日 | ||||||
| 日付 | 2015-05-28 | |||||
| 日付タイプ | Issued | |||||
