Development of a Novel Histone Deacetylase-Targeted Near-Infrared Probe for Hepatocellular Carcinoma Imaging and Fluorescence Image-Guided Surgery.

Autor:	Tang, Chu, Du, Yang, Liang, Qian, Cheng, Zhen, Tian, Jie
Předmět:	COMPUTER-assisted surgery HEPATOCELLULAR carcinoma FLUORESCENCE SURGICAL excision FLUORESCEIN isothiocyanate BENZENE derivatives RESEARCH INDOLE compounds LIVER tumors ANIMAL experimentation RESEARCH methodology CELL physiology CANCER relapse APOPTOSIS MEDICAL cooperation EVALUATION research DIAGNOSTIC imaging COMPARATIVE studies RESEARCH funding FLUORESCENT dyes CELL lines MICE
Zdroj:	Molecular Imaging & Biology; Jun2020, Vol. 22 Issue 3, p476-485, 10p
Abstrakt:	Purpose: Hepatocellular carcinoma (HCC) is a common cancer worldwide, and complete surgical resection of diseased tissue is a reliable strategy to cure cancer. Fluorescence image-guided surgery is a promising tool for surgeons to identify and remove malignant lesions. While non-targeted fluorescent dyes have been used for HCC diagnosis and resection, insufficient specificity and false positive uptake from inflammatory tissue result in a high recurrence rate or excessive excision of healthy liver tissue. To circumvent these problems, we focused on developing novel tumor-specific targeting probe to selectively illuminate cancer region during surgery. Given overexpression of histone deacetylases (HDACs) in HCC and many other cancers, HDAC-targeted imaging has been emerged as a promising tool for tumor detection.Procedures: Recently, high expression of HDACs, in particular HDAC6, has been observed in tumor samples of HCC patient, and a few HDAC inhibitors, including FDA-approved suberoylanilide hydroxamic acid (SAHA), display potent antitumor effect on HCC. Correspondingly, in this study, we utilized a small molecule SAHA with the high HDAC-binding affinity as the HCC-specific targeting ligand to develop HDAC-targeted fluorescence probe for HCC detection and fluorescence image-guided resection.Results: In in vitro imaging, SAHA was labelled with fluorescein isothiocyanate (FITC) to evaluate targeting property, and the imaging results demonstrated that FITC-SAHA was specific uptake by HCC Bel-7402 cells. In in vivo imaging, near infrared fluorescence dye IRDye800CW-labelled SAHA (NIR probe IRDye800CW-SAHA) showed rapid tumor accumulation with high tumor-to-background contrast on both the subcutaneous and orthotopic HCC mouse tumor models. Furthermore, the orthotopic HCC was successfully resected by the IRDye800CW-SAHA fluorescence image-guided surgery. Moreover, IRDye800CW-SAHA showed no toxicity toward healthy tissues.Conclusions: Our results indicate that IRDye800CW-SAHA is a clinical translatable probe for HCC detection and resection. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink