title: In vivo imaging of tumor apoptosis using histone H1-targeting peptide.
abstract: In vivo imaging of apoptosis could allow monitoring of tumor response to cancer treatments such as chemotherapy. Using phage display, we identified the CQRPPR peptide, named ApoPep-1(Apoptosis-targeting Peptide-1), that was able to home to apoptotic and necrotic cells in tumor tissue. ApoPep-1 also bound to apoptotic and necrotic cells in culture, while only little binding to live cells was observed. Its binding to apoptotic cells was not dependent on calcium ion and not competed by annexin V. The receptor for ApoPep-1 was identified to be histone H1 that was exposed on the surface of apoptotic cells. In necrotic cells, ApoPep-1 entered the cells and bound to histone H1 in the nucleus. The imaging signals produced during monitoring of tumor apoptosis in response to chemotherapy was enhanced by the homing of a fluorescent dye- or radioisotope-labeled ApoPep-1 to tumor treated with anti-cancer drugs, whereas its uptake of the liver and lung was minimal. These results suggest that ApoPep-1 holds great promise as a probe for in vivo imaging of apoptosis, while histone H1 is a unique molecular signature for this purpose.
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Purushotham
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Na
authors.forename: Hyekyung
authors.initials: H
authors.lastname: Park
authors.forename: Sun-Jeong
authors.initials: SJ
authors.lastname: Oh
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Eungbae
authors.initials: E
authors.lastname: Lee
authors.forename: Byung Chae
authors.initials: BC
authors.lastname: Cho
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Song
authors.forename: Moon-Chang
authors.initials: MC
authors.lastname: Baek
authors.forename: Wonjung
authors.initials: W
authors.lastname: Kwak
authors.forename: Jeongsoo
authors.initials: J
authors.lastname: Yoo
authors.forename: Allan S
authors.initials: AS
authors.lastname: Hoffman
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009336:Necrosis; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D049268:Positron-Emission Tomography; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006657:Histones; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C578342:cysteinyl-glutaminyl-arginyl-prolyl-prolyl-arginine