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Development of 1-N-[11C]-Methyl-L- and -D-Tryptophan for Pharmacokinetic Imaging of the Immune Checkpoint Inhibitor 1-Methyl-Tryptophan
https://repo.qst.go.jp/records/71871
https://repo.qst.go.jp/records/718717a696ad5-6f22-4d44-93f5-581743cdd8e0
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-11-25 | |||||
| タイトル | ||||||
| タイトル | Development of 1-N-[11C]-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_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 |
Xie, Lin
× Xie, Lin× Maeda, Jun× Kumata, Katsushi× Yui, Joji× Zhang, Yiding× Hatori, Akiko× Nengaki, Nobuki× Wakizaka, Hidekatsu× Fujinaga, Masayuki× 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× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: 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) (1). A long-standing debate exists in immunology and oncology: which stereoisomer has the potential of antitumor immunotherapy (2). As a first step to disentangle the potential and explore the possibility of pharmacokinetic imaging in immunotherapy, we here developed two novel radioprobes, 1-N-[11C]methyl-L- and -D-tryptophan ([11C]L-1MTrp and [11C]D-1-MTrp), without modifying the chemical structures of the two isomers, and delineated their pharmacokinetic imaging in whole body. 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. The pharmacokinetics of the L and D isomers were tracked using dynamic PET/CT scans and biodistribution study after the radioprobes injection. Results: [11C]L-1MTrp and [11C]D-1MTrp were obtained with radiochemical yields of 47 ± 6.3% (decay-corrected, based on [11C]CO2), a radiochemical purity of > 98%, specific activity of 47130 GBq/μmol, and high enantiomeric purity. PET/CT imaging in rats revealed that for [11C]L-1MTrp, the highest distribution of radioactivity was observed in the pancreas, while for [11C]D-1MTrp, it was observed in the kidney (Fig. 1). Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. Conclusion: Both [11C]L-1MTrp and [11C]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. |
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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 | Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry | |||||
| 発表年月日 | ||||||
| 日付 | 2015-11-09 | |||||
| 日付タイプ | Issued | |||||
