title: Copper-Free Click for PET: Rapid 1,3-Dipolar Cycloadditions with a Fluorine-18 Cyclooctyne.
abstract: The strain-promoted click 1,3-dipolar cycloaddition reactions involving azides and cyclooctynes for the synthesis of triazoles offer the advantage of being able to be performed in biological settings via copper-free chemistries. While strained reagents conjugated to optical dyes and radiometal conjugates have been reported, cyclooctyne reagents labeled with fluorine-18 ((18)F) and radiochemically evaluated in a copper-free click reaction have yet to be explored. This report describes the conversion of a bifunctional azadibenzocyclooctyne (ADIBO) amine to the (18)F-labeled cyclooctyne 4, the subsequent fast copper-free 1,3-dipolar cycloaddition reaction with alkyl azides at 37 °C (>70% radiochemical conversion in 30 min), and biological evaluations (serum stability of >95% at 2 h). These findings demonstrate the excellent reactivity of the (18)F-labeled cyclooctyne 4 with readily available azides that will allow future work focusing on rapid copper-free in vitro and in vivo click chemistries for PET imaging using (18)F-labeled cyclooctyne derivatives of ADIBO.
authors.affiliation: Department of Biomedical Engineering, Division of Hematology/Oncology, Department of Internal Medicine, and Center for Molecular and Genomic Imaging, University of California , Davis, California 95616, United States.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carpenter
authors.affiliation: Department of Biomedical Engineering, Division of Hematology/Oncology, Department of Internal Medicine, and Center for Molecular and Genomic Imaging, University of California , Davis, California 95616, United States.
authors.forename: Sven H
authors.initials: SH
authors.lastname: Hausner
authors.affiliation: Department of Biomedical Engineering, Division of Hematology/Oncology, Department of Internal Medicine, and Center for Molecular and Genomic Imaging, University of California , Davis, California 95616, United States.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Sutcliffe
keywords: Copper-free click chemistry; cycloaddition; cyclooctyne; fluorine-18; positron emission tomography