Production of a Novel Fluorine-18 Labeled Silver Species Derived from [18F]HF

14 Objectives: Our group previously communicated a new method to produce a fluorine-18 labeled Fe complex derived from [18F]HF for the regioselective radiosynthesis of [18F]fluorohydrins.(1) Through extensive screening we have now demonstrated that [18F]HF can also be trapped with silver to form a novel fluorine-18 labeled Ag species. Based on existing precedent and preliminary studies, it is anticipated that this new reagent will be competent in the radiofluorination of organic molecules including azine derivatives, a naturally abundant class of heterocycle.(2) Methods: Fluorine-18 was produced in a cyclotron via the 18O(p, n)18F nuclear reaction and trapped on a Waters QMA SepPak Light preconditioned with 0.5M KOTf and anhydrous MeCN. Various acids, at different concentrations in MeCN were manually screened as fluoride elutants, which were delivered into a vial containing a silver salt. The resulting mixture was dried at 80 oC, producing the target fluorine-18 labeled Ag reagent. For radiofluorination screens, the Ag species (AgxO) was redissolved in anhydrous MeCN and an organic substrate (40 µmol) was added before stirring at 80 oC for 30 min and analysis via radio-TLC and radio-HPLC. Results: Acids including trifluoroacetic acid, methanesulfonic acid, and tetrafluoroboric acid dissolved in anhydrous MeCN at various concentrations were successfully utilized to elute [18F]fluoride from a QMA cartridge to produce volatile [18F]HF, which was treated directly with a silver salt. A standard protocol involving the use of 40 µmol silver salt has been adopted, although Ag loadings as low as 4 µmol are possible. Following azeotropic drying, a fluorine-18 labeled Ag species was successfully synthesized as confirmed by control experiments. As an elutant, 0.5M MsOH outperformed other acids investigated in this study and enabled an overall fluorine-18 recovery of 45% (n = 2). Although recoveries using 1.0M trifluoroacetic acid were lower (32%, n=2), treatment of the fluorine-18 labeled Ag species derived from this acid with quinoline derivatives in refluxing MeCN led to the formation of a new, fluorine-18 labeled organic species, which was not observed using other acids. Full characterization of these compounds will be reported in due course. Conclusions: We have successfully synthesized a novel, fluorine-18 labeled silver species via acidic elutions of [18F]fluoride from a QMA followed by trapping with a silver salt. This reagent offers a new approach to investigate [18F]HF, which has a unique reactivity profile to more common sources of nucleophilic fluorine-18 (e.g. [18F]KF) and has seldom been investigated in sharp contrast to the corresponding fluorine-19 analog. Preliminary investigations indicate that this Ag reagent can be used to functionalize organic molecules and the application of this reagent to fluorine-18 labeling is currently underway. Acknowledgements: This work was supported by NIH (R01EB021155). References: 1. Verhoog S, Brooks AF, Winton WP, Viglianti BL, Sanford MS, Scott PJH. Ring Opening of Epoxides with [18F]FeF Species to Produce [18F]Fluorohydrin PET Imaging Agents. Chem Commun.2019, 55, 6361-6364.2. Fier PS, Hartwig JF. Selective C-H Fluorination of Pyridines and Diazines Inspired by a Classic Amination Reaction. Science, 2013, 342, 956-60.