摘要：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 -11C-methyl- l - and - d -tryptophan (11C- l -1MTrp and 11C- d -1MTrp), without modifying the chemical structures of the two isomers, and investigated their utility for pharmacokinetic imaging of the whole body. 11C- l -1MTrp and 11C- d -1MTrp were synthesized rapidly 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. Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. 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.
