Abstract 4120: A novel HDAC-targeted probe for triple-negative breast tumor imaging

Abstract

Abstract Purpose: Due to lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2), there was no specific imaging probes can be applied to detect triple-negative breast cancers (TNBCs). Currently, several lines of evidences support that overexpression of histone deacetylases (HDACs) has been associated with TNBC. Here, we sought to develop HDAC-targeted probe for TNBC imaging. Experimental Design: The pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was chosen as the targeting ligand, and was labeled with a near-infrared dye IRDye800CW for the development of HDAC-targeted probe IRDye800CW-SAHA. Subsequently, HDAC binding affinity and specificity of probe IRDye800CW-SelSA to TNBC MDA-MB-231 cells was evaluated by HDAC inhibition assay, flow cytometry and confocal laser microscope experiments. Moreover, the in vivo fluorescence molecular imaging (FMI) was performed to monitor the biodistribution and tumor targeting effects of the probe in MDA-MB-231 tumor xenografts. Results: The fluorescence probe IRDye800CW-SAHA was successfully developed, and conjugating IRDye800CW to SAHA did not alter the HDAC binding affinity. The cellular uptake and the fluorescence intensity of probe on MDA-MB-231 cells were significantly higher compared to normal MCF-10A cells (P < 0.05). Meanwhile, the cellular uptake of probe can be effectively blocked by co-incubation with SAHA. The in vivo imaging results showed that IRDye800CW-SelSA was able to target tumor rapidly, and the tumor to normal tissue (T/N) fluorescence intensity ratio reached the peak around 12 h (T/N = 3.4). Conclusions: Our study demonstrated that IRDye800CW-SAHA is an efficient probe for the targeted imaging of TNBC and may possess clinical translation in the future. CT and YD contributed equally to this work Citation Format: Chu Tang, Yang Du, Jie Tian. A novel HDAC-targeted probe for triple-negative breast tumor imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4120.