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

doi:10.1007/s11307-019-01389-4

	Development of a Novel Histone Deacetylase-Targeted Near-Infrared Probe for Hepatocellular Carcinoma Imaging and Fluorescence Image-Guided Surgery
	Tang, Chu1,2 ; Du, Yang2,3,4 ; Liang, Qian2 ; Cheng, Zhen 5,6; Tian, Jie 1,2,3,4,7
发表期刊	MOLECULAR IMAGING AND BIOLOGY
ISSN	1536-1632
	2020-06-01
卷号	22 期号:3 页码:476-485
通讯作者	Cheng, Zhen(zcheng@stanford.edu) ; Tian, Jie(jie.tian@ia.ac.cn)
摘要	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.
关键词	Specific targeting probe Histone deacetylase Fluorescence imaging Hepatocellular carcinoma Fluorescence image-guided surgery
DOI	10.1007/s11307-019-01389-4
关键词[WOS]	IN-VIVO ; INDOCYANINE GREEN ; PROGRESSION ; ACID ; INHIBITOR ; RESECTION ; RECEPTOR ; GLIOMAS ; CANCER ; CELLS
收录类别	SCI
语种	英语
WOS研究方向	Radiology, Nuclear Medicine & Medical Imaging
WOS类目	Radiology, Nuclear Medicine & Medical Imaging
WOS记录号	WOS:000535707700002
出版者	SPRINGER
七大方向——子方向分类	医学影像处理与分析
引用统计	被引频次：37[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/39555
专题	中国科学院分子影像重点实验室
通讯作者	Cheng, Zhen; Tian, Jie
作者单位	1.Xidian Univ, Engn Res Ctr Mol & Neuro Imaging, Sch Life Sci & Technol, Minist Educ, Xian 710126, Shaanxi, Peoples R China 2.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, State Key Lab Management & Control Complex Syst, Beijing 100190, Peoples R China 3.Beijing Key Lab Mol Imaging, Beijing 100190, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100080, Peoples R China 5.Stanford Univ, Stanford Canc Early Detect, Canary Ctr, Mol Imaging Program Stanford MIPS,Dept Radiol, Stanford, CA 94305 USA 6.Stanford Univ, Stanford Canc Early Detect, Canary Ctr, BioX Program, Stanford, CA 94305 USA 7.Beihang Univ, Beijing Adv Innovat Ctr Big Data Based Precis Med, Beijing 100191, Peoples R China
第一作者单位	中国科学院自动化研究所
通讯作者单位	中国科学院自动化研究所; 中国科学院分子影像重点实验室
推荐引用方式 GB/T 7714	Tang, Chu,Du, Yang,Liang, Qian,et al. Development of a Novel Histone Deacetylase-Targeted Near-Infrared Probe for Hepatocellular Carcinoma Imaging and Fluorescence Image-Guided Surgery[J]. MOLECULAR IMAGING AND BIOLOGY,2020,22(3):476-485.
APA	Tang, Chu,Du, Yang,Liang, Qian,Cheng, Zhen,&Tian, Jie.(2020).Development of a Novel Histone Deacetylase-Targeted Near-Infrared Probe for Hepatocellular Carcinoma Imaging and Fluorescence Image-Guided Surgery.MOLECULAR IMAGING AND BIOLOGY,22(3),476-485.
MLA	Tang, Chu,et al."Development of a Novel Histone Deacetylase-Targeted Near-Infrared Probe for Hepatocellular Carcinoma Imaging and Fluorescence Image-Guided Surgery".MOLECULAR IMAGING AND BIOLOGY 22.3(2020):476-485.