Iodonium Ylide Mediated Radiofluorination of ¹⁸F-FPEB and Validation for Human Use

Abstract

Translation of new methodologies for labeling non-activated aromatic molecules with fluorine-18 remains a challenge. Here, we report a one-step, regioselective, metal-free ¹⁸F-labeling method that employs a hypervalent iodonium(III) ylide precursor, to prepare the radiopharmaceutical ¹⁸F-FPEB. Methods: Automated radiosynthesis of ¹⁸F-FPEB was achieved by reaction of the ylide precursor (4 mg) with ¹⁸F-NEt4F in DMF at 80 °C for 5 minutes, and formulated for injection within 1 hour. Results: ¹⁸F-FPEB was synthesized in 15 – 25% (n = 3) uncorrected radiochemical yields relative to ¹⁸F-fluoride, with specific activities of 666 ± 51.8 GBq/μmol (18 ± 1.4 Ci/μmol) at the end-ofsynthesis (EOS) and was validated for human use. Conclusion: Radiofluorination of iodonium (III) ylides proved to be an efficient radiosynthetic strategy for synthesis of ¹⁸Flabeled radiopharmaceuticals.