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

Currently, only a few F-18-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 F-18-radiolabeling methodology based on organophosphine fluoride acceptors. The high water tolerance for this isotope-exchange-based F-18-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 [F-18/19] di-tert-butyl-organofluorophosphine and its derivatives used as F-18-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 F-18-radiolabeling pathway, enabling further widespread application of F-18.