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Strain-Promoted Catalyst-Free Click Chemistry for Rapid Construction of 64Cu-Labeled PET Imaging Probes

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journal contribution
posted on 13.12.2012, 00:00 by Kai Chen, Xinlu Wang, Wei-Yu Lin, Clifton K.-F. Shen, Li-Peng Yap, Lindsey D. Hughes, Peter S. Conti
A rapid, efficient, and catalyst-free click chemistry method for the construction of 64Cu-labeled PET imaging probes was reported based on the strain-promoted aza-dibenzocyclooctyne ligation. This new method was exemplified in the synthesis of 64Cu-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 64Cu radiolabeling procedure under the conventional Cu-catalyzed 1,3-dipolar cycloaddition condition. The new strategy is simple and robust, and the resultant 64Cu-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” 64Cu-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.