@misc{oai:repo.qst.go.jp:00071732,
 author = {Kumata, Katsushi and Xie, Lin and Yui, Joji and Hatori, Akiko and Zhang, Yiding and Nengaki, Nobuki and Fujinaga, Masayuki and Yamasaki, Tomoteru and Shimoda, Yoko and Maeda, Jun and Zhang, Ming-Rong and 熊田 勝志 and 謝 琳 and 由井 譲二 and 羽鳥 晶子 and 張 一鼎 and 念垣 信樹 and 藤永 雅之 and 山崎 友照 and 下田 陽子 and 前田 純 and 張 明栄},
 month = {May},
 note = {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., 21st International Symposium on Radiopharmaceutical Sciences},
 title = {Radiosynthesis and pharmacokinetic comparison of 1-N-[11C]methyl]-L- and -D-tryptophan},
 year = {2015}
}