Radiofluorination of an anionic, azide-functionalized teroligomer by copper-catalyzed azide-alkyne cycloaddition

This study describes the synthesis, radiofluorination and purification of an anionic amphiphilic teroligomer developed as stabilizer for siRNA-loaded calcium phosphate nanoparticles (CaP-NP). As the stabilizing amphiphile accumulates on nanoparticle surfaces, the fluorine-18 labeled polymer should enable to track the distribution of the CaP-NP in brain tumors after ap-plication by convection-enhanced delivery. At first, an unmodified teroligomer was synthesized with a number average molecular weight of 4550 ± 20 Da by free radical polymerization of a de-fined composition of methoxy-PEG-monomethacrylate, tetradecyl acrylate and maleic anhy-dride. Subsequent derivatization of anhydrides with azido-TEG-amine provided an azido func-tionalized polymer precursor (o14PEGMA-1) for radiofluorination. The 18F-labeling was accom-plished by copper-catalyzed cycloaddition of o14PEGMA-1 with the diethylene glycol - alkyne substituted heteroaromatic prosthetic group [18F]2 which was synthesized with a radiochemical yield (RCY) of about 38% within 60 min using a radiosynthesis module. The 18F-labeled polymer [18F]fluoro-o14PEGMA-2 was obtained after a short reaction time of 2-3 min by using CuSO4/sodium ascorbate at 90 °C. Purification was performed by solid-phase extraction on an anion-exchange cartridge followed by size-exclusion chromatography to obtain [18F]fluoro-o14PEGMA-2 with a high radiochemical purity and an RCY of about 15%.