title: In vivo near-infrared fluorescence imaging of apoptosis using histone H1-targeting peptide probe after anti-cancer treatment with cisplatin and cetuximab for early decision on tumor response.
abstract: Early decision on tumor response after anti-cancer treatment is still an unmet medical need. Here we investigated whether in vivo imaging of apoptosis using linear and cyclic (disulfide-bonded) form of ApoPep-1, a peptide that recognizes histone H1 exposed on apoptotic cells, at an early stage after treatment could predict tumor response to the treatment later. Treatment of stomach tumor cells with cistplatin or cetuximab alone induced apoptosis, while combination of cisplatin plus cetuximab more efficiently induced apoptosis, as detected by binding with linear and cyclic form of ApoPep-1. However, the differences between the single agent and combination treatment were more remarkable as detected with the cyclic form compared to the linear form. In tumor-bearing mice, apoptosis imaging was performed 1 week and 2 weeks after the initiation of treatment, while tumor volumes and weights were measured 3 weeks after the treatment. In vivo fluorescence imaging signals obtained by the uptake of ApoPep-1 to tumor was most remarkable in the group injected with cyclic form of ApoPep-1 at 1 week after combined treatment with cisplatin plus cetuximab. Correlation analysis revealed that imaging signals by cyclic ApoPep-1 at 1 week after treatment with cisplatin plus cetuximab in combination were most closely related with tumor volume changes (r2 = 0.934). These results demonstrate that in vivo apoptosis imaging using Apopep-1, especially cyclic ApoPep-1, is a sensitive and predictive tool for early decision on stomach tumor response after anti-cancer treatment.
authors.affiliation: Department of Biochemistry and Cell Biology and School of Medicine, Kyungpook National University, Daegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Jung
authors.affiliation: Department of Plastic Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Min Kyu
authors.initials: MK
authors.lastname: Jung
authors.affiliation: Department of Biochemistry and Cell Biology and School of Medicine, Kyungpook National University, Daegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Korea.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Cell Biology and School of Medicine, Kyungpook National University, Daegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Korea.
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D002945:Cisplatin / Q000494:pharmacology*; D003657:Decision Making; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007259:Infrared Rays; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D061848:Optical Imaging; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism; D055550:Protein Stability; D013274:Stomach Neoplasms / Q000473:pathology; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D006657:Histones; D015335:Molecular Probes; D009842:Oligopeptides; D010456:Peptides, Cyclic; D000068818:Cetuximab; D002945:Cisplatin