Surfactants Accelerate Isotope Exchange-Based ¹⁸F-Fluorination in Water

Radiochemical yields (RCYs) of isotope exchange-based ¹⁸F-fluorination of non-carbon-centered substrates in water are rationally enhanced by adding surfactants, which increases both the rate constant k and local reactant concentrations. Among 12 surfactants, the cationic surfactant cetrimonium bromide (CTAB) and two nonionic surfactants (Tween 20 and Tween 80) were selected for their superior catalytic effects, namely, electrostatic effects or solubilization effects. For a model substrate, bis(4-methoxyphenyl)phosphinic fluoride, the ¹⁸F-fluorination rate constant (k) increased up to 7-fold, while its saturation concentration rose up to 15-fold due to micelle formation, encapsulating 70-94% of the substrate. With 30.0 mmol/L CTAB, the required ¹⁸F-labeling temperature of a typical organofluorosilicon prosthesis ([¹⁸F]SiFA) decreased from 95 °C to room temperature, achieving an RCY of 22%. For an E[c(RGDyK)]₂-derived peptide tracer with an organofluorophosphine prosthesis, the RCY in water at 90 °C achieved 25%, correspondingly increasing the molar activity (A_m). After high-performance liquid chromatography (HPLC) or solid-phase purification, the residual selected surfactant concentrations in the tracer injections were well below the FDA DII (Inactive Ingredient Database) limits or the LD50 in mice.