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

J Med Chem. 2020 Nov 12;63(21):12693-12706. doi: 10.1021/acs.jmedchem.0c00997. Epub 2020 Oct 21.

Abstract

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 18F-19F 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 (t1/2 = 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 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 β-diketone molecules.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Boron / chemistry*
  • Fluorine / chemistry*
  • Fluorine / metabolism
  • Fluorine Radioisotopes / chemistry
  • Fluorine Radioisotopes / metabolism
  • Half-Life
  • Isotope Labeling
  • Ketones / chemistry*
  • Magnetic Resonance Imaging
  • Mice
  • Positron-Emission Tomography
  • Rabbits
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / metabolism
  • Whole Body Imaging

Substances

  • Fluorine Radioisotopes
  • Ketones
  • Radiopharmaceuticals
  • Fluorine
  • Fluorine-18
  • Boron