With the growing importance of ¹⁸F-labeled radiotracers as effective diagnostic tools for various diseases, there is considerable interest in establishing a rapid, reliable, and robust approach to ¹⁸F-radiolabeling for positron emission tomography (PET) in molecular imaging. There is an unmet need for an effective practice to install fluorine-18 into diverse chemical frameworks to functionalize the target compounds for use in image-based drug development. The fluorosulfuryl group, utilized in sulfur(VI) fluoride exchange (SuFEx), serves as a versatile functional moiety that has been extensively explored in both pharmaceutical and materials research. The use of cyclotron-produced [¹⁸F]fluoride ion to activate various fluorosulfuryl moieties enhances the new possibilities for innovative approaches in drug discovery. Here, we report a streamlined method for isotopic exchange at the sulfonyl core between ¹⁹F and radioactive ¹⁸F. To overcome the issues associated with the short physical half-life of ¹⁸F (109.7 min), we developed the azeotropic drying-free and cryptand-free radiofluorination by direct use of ¹⁸F-eluent from QMA (quaternary methyl ammonium) cartridge. Various aryl [¹⁸F]fluorosulfates and sulfamoyl [¹⁸F]fluorides were synthesized through ¹⁹F/¹⁸F isotopic exchange, even with heavily hydrated fluorine-18 source (with water content up to 5% in organic reaction medium). The late-stage isotopic activation provided diverse ¹⁸F-labeled aryl fluorosulfates and sulfamoyl fluorides at radiochemical conversion (RCC) up to 92%. This labeling technique offers a reliable way to incorporate ¹⁸F into sulfur-oxygen and sulfur-nitrogen frameworks. It eliminates the need for time-consuming azeotropic drying and simplifies the downstream quality control process without using cryptands. This newly devised method provides a simple and practical means to produce diverse ¹⁸F-labeled SuFEx compounds, which holds promise for use in PET imaging.

Jinsil Jeong

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