One-Step, Rapid, F-F Isotopic Exchange Radiolabeling of Difluoro-dioxaborinins: Substituent Effect on Stability and Applications.

The β-diketone moiety is commonly present in many anticancer drugs, antibiotics, and natural products. We describe a general method for radiolabeling β-diketone-bearing molecules with fluoride-18. Radiolabeling was carried out via F-F isotopic exchange on nonradioactive difluoro-dioxaborinins, which were generated by minimally modifying the β-diketone as a difluoroborate. Radiochemistry was one-step, rapid (<10 min), and high-yielding (>80%) and proceeded at room temperature to accommodate the half-life of F-18 ( = 110 min). High molar activities (7.4 Ci/μmol) were achieved with relatively low starting activities (16.4 mCi). It was found that substituents affected both the solvolytic stability and fluorescence properties of difluoro-dioxaborinins. An F-18 radiolabeled difluoro-dioxaborinin probe that was simultaneously fluorescent showed sufficient stability for positron emission tomography (PET)/fluorescence imaging in mice, rabbits, and patients. These findings will guide the design of probes with specific PET/fluorescence properties; the development of new PET/fluorescence dual-modality reporters; and accurate tracking of β-diketone molecules.