@misc{oai:repo.qst.go.jp:00071871,
 author = {Xie, Lin and Maeda, Jun and Kumata, Katsushi and Yui, Joji and Zhang, Yiding and Hatori, Akiko and Nengaki, Nobuki and Wakizaka, Hidekatsu and Fujinaga, Masayuki and Zhang, Ming-Rong and 謝 琳 and 前田 純 and 熊田 勝志 and 由井 譲二 and 張 一鼎 and 羽鳥 晶子 and 念垣 信樹 and 脇坂 秀克 and 藤永 雅之 and 張 明栄},
 month = {Nov},
 note = {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 47130 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., Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry},
 title = {Development of 1-N-[11C]-Methyl-L- and -D-Tryptophan for Pharmacokinetic Imaging of the Immune Checkpoint Inhibitor 1-Methyl-Tryptophan},
 year = {2015}
}