One-Step, Rapid, 18F–19F Isotopic Exchange Radiolabeling of Difluoro-dioxaborinins: Substituent Effect on Stability and In Vivo Applications
| Autor: | Richard Ting, Haluk Sayman, Fuad Nurili, Feifei An, Omer Aras, Hüseyin Çakıroğlu, Zahide Ozer |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Fluorine Radioisotopes
General method Substituent One-Step digestive system 01 natural sciences Article Mice 03 medical and health sciences chemistry.chemical_compound In vivo Drug Discovery Animals Moiety Molecule Whole Body Imaging Boron 030304 developmental biology 0303 health sciences Chemistry Fluorine Ketones Magnetic Resonance Imaging Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Isotope Labeling Positron-Emission Tomography Molecular Medicine Rabbits Radiopharmaceuticals Half-Life |
| Zdroj: | J Med Chem |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.0c00997 |
| Popis: | 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 is carried out via (18)F-(19)F isotopic exchange on non-radioactive difluoro-dioxaborinins, which are generated by minimally modifying the β-diketone as a difluoroborate. Radiochemistry is one-step, rapid (< 10 min), high-yielding (> 80%), and proceeds at room temperature to accommodate the half-life of F-18 (t(1/2) = 110 min). High molar activities (7.4 Ci/μmol) were achieved with relatively low starting activities (16.4 mCi). It was found that substituents affect both the solvolytic stability and fluorescence properties of difluoro-dioxaborinins. An F-18 radiolabeled difluoro-dioxaborinin probe that is simultaneously fluorescent showed sufficient stability for in vivo 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|