title: Novel (64)Cu-Labeled CUDC-101 for in Vivo PET Imaging of Histone Deacetylases.
abstract: 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.
authors.affiliation: Department of Translational Imaging, The Methodist Hospital Research Institute , Houston, Texas 77030, United States.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Translational Imaging, The Methodist Hospital Research Institute , Houston, Texas 77030, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou 510530, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Translational Imaging, The Methodist Hospital Research Institute , Houston, Texas 77030, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
keywords: 64Cu radiolabeling; CUDC-101; PET imaging probe; histone deacetylases inhibitors; triple-negative breast cancer