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

[¹⁸F]Gln-OSO₂F, [¹⁸F]Arg-OSO₂F, and [¹⁸F]FSY-OSO₂F were designed by introducing sulfonyl ¹⁸F-fluoride onto glutamine, arginine, and tyrosine, respectively. [¹⁸F]FSY-OSO₂F can be prepared directly by sulfur ¹⁸F-fluoride exchange, while [¹⁸F]Gln-OSO₂F and [¹⁸F]Arg-OSO₂F require a two-step labeling method. Those tracers retain their typical transport characteristics for unmodified Amino acids. Both PET imaging and biodistribution confirmed that [¹⁸F]FSY-OSO₂F visualized MCF-7 and 22Rv1 subcutaneous tumors with high contrast, and its tumor-to-muscle ratio was better than that of [¹⁸F]FET. However, [¹⁸F]Gln-OSO₂F and [¹⁸F]Arg-OSO₂F 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 ¹⁸F-fluoride exchange Click Chemistry in the design of radioactive sulfonyl fluoride Amino acids is feasible and offers significant advantages.