One-Step, Rapid, <sup>18</sup>F–<sup>19</sup>F Isotopic Exchange Radiolabeling of\nDifluoro-dioxaborinins: Substituent\nEffect on Stability and <i>In Vivo</i> Applications

The\nβ-diketone moiety is commonly present in many anticancer\ndrugs, antibiotics, and natural products. We describe a general method\nfor radiolabeling β-diketone-bearing molecules with fluoride-18.\nRadiolabeling was carried out via <sup>18</sup>F–<sup>19</sup>F isotopic exchange on nonradioactive difluoro-dioxaborinins, which\nwere generated by minimally modifying the β-diketone as a difluoroborate.\nRadiochemistry was one-step, rapid (<10 min), and high-yielding\n(>80%) and proceeded at room temperature to accommodate the half-life\nof F-18 (<i>t</i><sub>1/2</sub> = 110 min). High molar activities\n(7.4 Ci/μmol) were achieved with relatively low starting activities\n(16.4 mCi). It was found that substituents affected both the solvolytic\nstability and fluorescence properties of difluoro-dioxaborinins. An\nF-18 radiolabeled difluoro-dioxaborinin probe that was simultaneously\nfluorescent showed sufficient stability for <i>in vivo</i> positron emission tomography (PET)/fluorescence imaging in mice,\nrabbits, and patients. These findings will guide the design of probes\nwith specific PET/fluorescence properties; the development of new\nPET/fluorescence dual-modality reporters; and accurate <i>in\nvivo</i> tracking of β-diketone molecules.