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

Radiochemicalyields (RCYs) of isotope exchange-based F-18-fluorinationof non-carbon-centered substrates in water are rationallyenhanced 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 nonionicsurfactants (Tween 20 and Tween 80) were selected for their superiorcatalytic effects, namely, electrostatic effects or solubilizationeffects. For a model substrate, bis(4-methoxy-phenyl)phosphinicfluoride, the F-18-fluorination rate constant (k) increased up to 7-fold, while its saturation concentration roseup to 15-fold due to micelle formation, encapsulating 70-94%of the substrate. With 30.0 mmol/L CTAB, the required F-18-labeling temperature of a typical organofluorosilicon prosthesis([F-18]SiFA) decreased from 95 degrees C to room temperature,achieving an RCY of 22%. For an E[c(RGDyK)](2)-derived peptidetracer with an organofluoro-phosphine prosthesis, the RCY inwater at 90 degrees C achieved 25%, correspondingly increasing themolar activity (A(m)). After high-performance liquid chromatography(HPLC) or solid-phase purification, the residual selected surfactantconcentrations in the tracer injections were well below the FDA DII(Inactive Ingredient Database) limits or the LD50 in mice.