Zude Chen
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School,
Title: Cell experiments and imaging assisted evaluation of a new histone deacetylase inhibitor cn133 in the Castration-Resistant Prostate
Biography
Biography: Zude Chen
Abstract
Purpose: The purpose of this work was to evaluate the effect of histone deacetylase (HDAC) inhibitor, CN133, on castration-resistance prostate cancer (CRPC) xenograft model and a possibility for quantifying this HDACi occupancy in this prostate cancer model using the HDAC PET/CT imaging probe, [11C]martinostat.
Methods: In the 22Rv1 xenograft model, we designed 5 groups of 10 mice bearing 22RV1 xenografts including vehicle, 25mg/kg, 50mg/kg SAHA or 1mg/kg and 5 mg/kg cn133, and the anti-tumor efficacy of CN133 was compared to the pan-HDAC inhibitor Suberoylanilide Hydroxamic Acid (SAHA).
We imaged 3 groups of 4 mice bearing 22RV1 xenografts before and 21 d after treatment with control vehicle, 1mg/kg and 5mg/kg CN133. Uptake on pre- and post-treatment imaging was measured and compared.
We also compared the abilities of our selective HDAC inhibitor, CN133, with pan-HDAC inhibitors, SAHA, in affecting prostate cancer cell proliferation, invasion, migration. AR-mediated target gene and target protein expression were assessed in 22RV1 prostate cancer cell lines by qPCR and western blot.
Result: Treatment of 22RV1 tumor-bearing nude mice with 1mg/kg cn133 led to a 50% reduction in