title: Identification of a Glypican-3-Binding Peptide for In Vivo Non-Invasive Human Hepatocellular Carcinoma Detection.
abstract: Early and accurate detection of hepatocellular carcinoma (HCC) is essential to improve the prognosis of patients and reduce the morbidity of surgical therapy. Glypican-3 (GPC3) is a protein abnormally expressed in HCC that has been identified as a serological and histochemical HCC marker. A novel peptide that specifically recognizes GPC3 will facilitate early detection of HCC and guide the treatment strategy. Herein, phage display screening technology is utilized to obtain a GPC3 binding peptide (GBP) using HCC cells expressing GPC3 in varying abundances. After seven rounds of panning, a peptide with sequence of THVSPNQGGLPS is identified with 735.2 ± 53.6 × 10-9m affinity to GPC3. The ability to target GPC3 in vivo is evaluated by intravenous injection of GBP labeled with a near-infrared dye, Cy5.5, into a HCC tumor-bearing mouse model. Significant high tumor accumulation (tumor/muscle ratio: 6.49 ± 0.55) of Cy5.5-GBP in HepG2 tumors is observed compared with that of the low GPC3 expressing prostate cancer cell line, PC3 (tumor/muscle ratio: 1.15 ± 0.32). By targeting GPC3, GBP differentiates tumor tissues from normal liver tissues in patients, suggesting a great clinical translation potency of GBP. Collectively, GBP demonstrates great potential for HCC detection via fluorescent imaging or histological staining.
authors.affiliation: 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.|Collaborative Innovation Center of Guangxi Biological Medicine and the, Medical and Scientific Research Center, Guangxi Medical University, Nanning 530000, China.
authors.forename: Zainen
authors.initials: Z
authors.lastname: Qin
authors.affiliation: 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.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Science, Jilin University, Changchun, 130000, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.forename: Guohao
authors.initials: G
authors.lastname: Wang
authors.affiliation: 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.forename: Xiangyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Surgery and Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: 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.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun, Jilin, 130033, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Gao
authors.affiliation: 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.|Department of Surgery and Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001435:Bacteriophages; D002232:Carbocyanines / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology; D002999:Clone Cells; D005453:Fluorescence; D053673:Glypicans / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008819:Mice, Nude; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D013194:Staining and Labeling; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; C105937:GPC3 protein, human; D053673:Glypicans; D010455:Peptides
keywords: fluorescent imaging; glypican-3; hepatocellular carcinoma; phage display