Strategies for reducing isotopic dilution in the synthesis of 18F-labeled polyfluorinated ethyl groups

Previous attempts to synthesize the alkylating agent 2,2,2-trifluoroethyl triflate labeled in the two position starting with the nucleophilic reaction of [18F]F− with ethyl bromodifluoroacetate revealed that considerable unlabeled ethyl trifluoroacetate was simultaneously produced, giving a specific activity of ≈ 0.04 GBq/μmol from 1.85 GBq [18F]F−. Two approaches were investigated here for reducing the amount of 19F released from the fluorinated substrate during the fluoro-debromination reaction: (a) distilling the halogenated ester through a functionalized Merrifieldʹs resin containing immobilized [18F]F− and (b) restraining the carboxylic functionality in an oxazoline ring before the fluoro-debromination with no-carrier-added [18F]F−. The specific activity of the isolated ethyl [2-18F]trifluoroacetate obtained by the resin method was increased to ≈ 0.4 GBq/μmol starting with the same amounts of [18F]F−. Use of the oxazoline required microwave treatment for fast radiolabeling (45–55% in 15 s) but, on the other hand, permitted large reductions in the amount of precursor used. Under optimal conditions, the specific activity was increased by a factor of ≈ 20 compared to the previous study. These results indicate the feasibility of this strategy for reducing isotopic dilution in the synthesis of such 18F-labeled polyfluorinated ethyl groups.