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

Abstract

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.