We report the design, synthesis, and biological evaluation of a 64Cu-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 64Cu. The resulting 64Cu-labeled compound 7 ([64Cu]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 [64Cu]7 to HDACs. Biodistribution and small-animal microPET/CT studies further showed that [64Cu]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, [64Cu]7 thus represents the first 64Cu-labeled PET HDAC imaging probe, which exhibits nanomolar range binding affinity and capability to imaging HDAC expression in triple-negative breast cancer in vivo.
- histone deacetylases inhibitors
- PET imaging probe
- triple-negative breast cancer
ASJC Scopus subject areas
- Organic Chemistry
- Drug Discovery