Design of Novel 18 F-Labeled Amino Acid Tracers Using Sulfur 18 F-Fluoride Exchange Click Chemistry.

[ 18 F]Gln-OSO 2 F, [ 18 F]Arg-OSO 2 F, and [ 18 F]FSY-OSO 2 F were designed by introducing sulfonyl 18 F-fluoride onto glutamine, arginine, and tyrosine, respectively. [ 18 F]FSY-OSO 2 F can be prepared directly by sulfur 18 F-fluoride exchange, while [ 18 F]Gln-OSO 2 F and [ 18 F]Arg-OSO 2 F require a two-step labeling method. Those tracers retain their typical transport characteristics for unmodified amino acids. Both PET imaging and biodistribution confirmed that [ 18 F]FSY-OSO 2 F visualized MCF-7 and 22Rv1 subcutaneous tumors with high contrast, and its tumor-to-muscle ratio was better than that of [ 18 F]FET. However, [ 18 F]Gln-OSO 2 F and [ 18 F]Arg-OSO 2 F poorly image MCF-7 subcutaneous tumors, possibly due to differences in the types and amounts of transporters expressed in tumors. All three tracers can visualize the U87MG glioma. According to our biological evaluation, none of the tracers evaluated in this study exhibited obvious defluorination, and subtle structural changes led to different imaging characteristics, indicating that the application of sulfur 18 F-fluoride exchange click chemistry in the design of radioactive sulfonyl fluoride amino acids is feasible and offers significant advantages.