We report the design, synthesis, and biological evaluation of a (64)Cu-labeled histone deacetylase (HDAC) imaging probe, which was obtained by introduction of metal chelator through click reaction of HDAC inhibitor CUDC-101 and then radiolabeled with (64)Cu. The resulting (64)Cu-labeled compound 7 ([(64)Cu]7) was identified as a positron emission tomography (PET) imaging probe to noninvasively visualize HDAC expression in vivo. Cell based competitive assay established the specific binding of [(64)Cu]7 to HDACs. Biodistribution and small-animal microPET/CT studies further showed that [(64)Cu]7 had high tumor to background ratio in the MDA-MB-231 xenograft model, a triple-negative breast cancer with high expression of HDACs. To our knowledge, [(64)Cu]7 thus represents the first (64)Cu-labeled PET HDAC imaging probe, which exhibits nanomolar range binding affinity and capability to imaging HDAC expression in triple-negative breast cancer in vivo.
Keywords: 64Cu radiolabeling; CUDC-101; PET imaging probe; histone deacetylases inhibitors; triple-negative breast cancer.