title: An HDAC-Targeted Imaging Probe LBH589-Cy5.5 for Tumor Detection and Therapy Evaluation.
abstract: Histone deacetylases (HDACs) are overexpressed in various cancers. In vivo imaging to measure the expression and functions of HDACs in tumor plays an important role for tumor diagnosis and HDAC-targeted therapy evaluation. The development of stable and highly sensitive HDAC targeting probe is highly desirable. Near-infrared (NIR) fluorescence optical imaging is a powerful technology for visualizing disease at the molecular level in vivo with high sensitivity and no ionizing radiation. We report here the design, synthesis, and bioactivity evaluation of LBH589-Cy5.5 for in vivo NIR fluorescence imaging of HDACs. The IC50 value of the resulting NIR probe to HDACs was determined to be 9.6 nM. In vitro fluorescence microscopic studies using a triple-negative breast cancer cell line, MDA-MB-231, established the binding specificity of LBH589-Cy5.5 to HDACs. An in vivo imaging study performed in MDA-MB-231 tumor xenografts demonstrated accumulation of the probe in tumor with good contrast from 2 h to 48 h postinjection. Furthermore, the fluorescent signal of LBH589-Cy5.5 in tumor was successfully blocked by coinjection of nonfluorescent LBH589 with the probe. In a following therapy evaluation study, the administration of SAHA, a clinically used HDAC inhibitor, decreased LBH589-Cy5.5 accumulation in tumor, demonstrating the potential application of LBH589-Cy5.5 for evaluating therapeutic response of HDAC inhibitors in cancer treatment.
authors.affiliation: †Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Meng
authors.affiliation: †Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: †Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ma
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Huan
authors.affiliation: †Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas 77030, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases
keywords: LBH589; NIR fluorescent imaging; histone deacetylases; therapy evaluation; triple-negative breast cancer