title: Strain-Promoted Catalyst-Free Click Chemistry for Rapid Construction of (64)Cu-Labeled PET Imaging Probes.
abstract: A rapid, efficient, and catalyst-free click chemistry method for the construction of (64)Cu-labeled PET imaging probes was reported based on the strain-promoted aza-dibenzocyclooctyne ligation. This new method was exemplified in the synthesis of (64)Cu-labeled RGD peptide for PET imaging of tumor integrin αvβ3 expression in vivo. The catalyst-free click chemistry reaction proceeded with a fast rate and eliminated the contamination problem of the catalyst Cu(I) ions interfering with the (64)Cu radiolabeling procedure under the conventional Cu-catalyzed 1,3-dipolar cycloaddition condition. The new strategy is simple and robust, and the resultant (64)Cu-labeled RGD probe was obtained in an excellent yield and high specific activity. PET imaging and biodistribution studies revealed significant, specific uptake of the "click" (64)Cu-labeled RGD probe in integrin αvβ3-positive U87MG xenografts with little uptake in nontarget tissues. This new approach is versatile, which warrants a wide range of applications for highly diverse radiometalated bioconjugates for radioimaging and radiotherapy.
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California , Los Angeles, California 90033, United States.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California , Los Angeles, California 90033, United States ; Department of Nuclear Medicine and PET-CT Center, Guangzhou General Hospital of Guangzhou Military Command , Guangzhou 510010, China.
authors.forename: Xinlu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California at Los Angeles , Los Angeles, California 90095, United States.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California at Los Angeles , Los Angeles, California 90095, United States.
authors.forename: Clifton K-F
authors.initials: CK
authors.lastname: Shen
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California , Los Angeles, California 90033, United States.
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Yap
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California , Los Angeles, California 90033, United States.
authors.forename: Lindsey D
authors.initials: LD
authors.lastname: Hughes
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California , Los Angeles, California 90033, United States.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
keywords: 64Cu radiolabeling; PET imaging probe; catalyst-free click chemistry; in vivo; integrin αvβ3