One-Step, Rapid, F-18-F-19 Isotopic Exchange Radiolabeling of Difluoro-dioxaborinins: Substituent Effect on Stability and In Vivo Applications

Abstract

The beta-diketone moiety is commonly present in many anticancer drugs, antibiotics, and natural products. We describe a general method for radiolabeling beta-diketone-bearing molecules with fluoride-18. Radiolabeling was carried out via F-18-F-19 isotopic exchange on nonradioactive difluoro-dioxaborinins, which were generated by minimally modifying the beta-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 (t(1/2) = 110 min). High molar activities (7.4 Ci/mu mol) 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 in vivo 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 in vivo tracking of beta-diketone molecules.