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

Abstract

Radiochemical yields (RCYs) of isotope exchange-based 18 F-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(4methoxyphenyl)phosphinic fluoride, the 18 F-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 18 F-labeling temperature of a typical organofluorosilicon prosthesis ([ 18 F]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.

“AquaF” Building Blocks for Water-Compatible SN2 18F-Fluorination of Small-Molecule Radiotracers

“…Hydrophilicity was an initial consideration in screening these building blocks, assessed through log S predicted by ALOGPS 2.1 . The log S values for 2 (−3.17), 7 (−2.40), and 16 (−0.47) were also determined based on previously measured saturation solubilities in pure water (0.17 g/L for 2 , 1.11 g/L for 7 , and 68.8 g/L for 16 ) . Building blocks 3 , 5 , 6 , 9 , 10 , 13 , and 15 , with log S values below −4, exhibited poor water solubilities.…”