title: Novel Glypican-3-Binding Peptide for in Vivo Hepatocellular Carcinoma Fluorescent Imaging.
abstract: Glypican-3 (GPC3) is a key member of the glypican family that is expressed on the cell surface by a glycosyl-phosphatidyl-inositol (GPI) anchor. It plays a significant role in hepatocellular carcinoma (HCC) development, angiogenesis, and metastasis. Most HCC overexpress GPC3, whereas little GPC3 can be detected in normal adult liver and benign liver lesions. Therefore, it is important to understand the function of GPC3 in HCC tumor development as the GPC3 ligand may facilitate detection of HCC. In this study, a 12-mer peptide with the sequence of DHLASLWWGTEL (denoted as TJ12P1) was identified by screening a phage display peptide library that demonstrated ideal GPC3 binding affinity. We used TJ12P1 conjugated with near-infrared fluorescent (NIFR) dye Cy5.5 for tumor imaging. After intravenous injection of the imaging agent, TJ12P1, xenografts of high GPC3 expressing hepatocellular carcinoma cell line, HepG2, demonstrated significantly higher tumor accumulation (tumor/muscle ratio: 3.98 ± 0.36) than those of low GPC3 expressing prostate cancer cell line, PC3 (tumor/muscle ratio: 2.03 ± 0.23). More importantly, GPC3 expression in tumor samples of patients could be visualized using TJ12P1, suggesting the potential use of this peptide as a probe for HCC detection. Our study has successfully identified a promising GPC3-binding peptide ligand for detecting the GPC3 expression in HCC not only in vitro but also in vivo by its noninvasive imaging.
authors: Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430000, China.
authors: Dongling
authors: D
authors: Zhu
authors: Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430000, China.
authors: Yushuang
authors: Y
authors: Qin
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen 361005, China.
authors: Jingjing
authors: J
authors: Wang
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen 361005, China.
authors: Liwen
authors: L
authors: Zhang
authors: Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430000, China.
authors: Sijuan
authors: S
authors: Zou
authors: Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430000, China.
authors: Xiaohua
authors: X
authors: Zhu
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen 361005, China.
authors: Lei
authors: L
authors: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D053673:Glypicans / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans