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Currently, only a few  18 F-radiolabeling methods were conducted in aqueous media, with non-macroelement fluoride acceptors and stringent conditions required. Herein, we describe a one-step non-solvent-biased, room-temperature-driven  18 F-radiolabeling methodology based on organophosphine fluoride acceptors. The high water tolerance for this isotope-exchange-based  18 F-labeling method is attributed to the kinetic and thermodynamic preference of F/F over the OH/F substitution based on computational calculations and experimental validation. Compact [ 18/19 F]di- tert -butyl-organofluorophosphine and its derivatives used as  18 F-labeling synthons exhibit excellent stability in vivo. The synthons are further conjugated to several biomolecular ligands such as c(RGDyk) and human serum albumin. The one-step labeled biomolecular tracers demonstrate intrinsic target imaging ability and negligible defluorination in vivo. The current method thus offers a facile and efficient  18 F-radiolabeling pathway, enabling further widespread application of  18 F.

Rapid one-step 18F-radiolabeling of biomolecules in aqueous media by organophosphine fluoride acceptors