title: Application of peptide displaying phage as a novel diagnostic probe for human lung adenocarcinoma.
abstract: Despite the increasing lung cancer-associated death rate, its therapy has been constrained by impasse of early diagnosis. To apply non-invasive imaging for potential cancer diagnosis system, we screened human lung adenocarcinoma-specific peptides using the phage display technique. For in vivo phage-displayed peptide screening, M13 phage library displaying 2.9 × 10(9) random peptides was injected through tail vein to lung adenocarcinoma cell-derived xenograft mouse model. Through four rounds of biopanning, a specific peptide sequence (CAKATCPAC) was screened out with the highest frequency and was named as Pep-1, and it was analyzed for its targeting ability as an imaging probe by in vitro competitive assay to test its cell-binding ability, immunohistochemical detection in the tumor tissue, and in vivo NIR fluorescent optical imaging. The specificity of Pep-1 toward lung cancer was ensured by in vivo imaging using xenograft animals of various cancer types. The results suggest that Pep-1 is a promising diagnostic lead molecule for rapid and accurate detection of human lung adenocarcinoma. In addition, it was found that the targeting ability was much enhanced by ionizing radiation in both cell-derived and patient-derived lung adenocarcinoma xenografts, suggesting the possibility of applying Pep-1 for prognostic diagnosis after radiotherapy. Taken together, this study suggests that Pep-1 possesses a specific-targeting ability for human lung adenocarcinoma and that this peptide could be directly used as a clinically applicable imaging probe.
authors.affiliation: Center for Development and Commercialization of Anti-cancer Therapeutics, Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea.|Asan Institute for Life Science, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea.
authors.forename: Kyoung Jin
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Center for Development and Commercialization of Anti-cancer Therapeutics, Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea.|Asan Institute for Life Science, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Korea Institute of Radiological and Medical Sciences, National Project to Establish Platform To Develop the New Concept Therapy, Seoul, 138-706, Korea.
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Chung
authors.affiliation: Center for Development and Commercialization of Anti-cancer Therapeutics, Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea.|Asan Institute for Life Science, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Ju
authors.affiliation: Center for Development and Commercialization of Anti-cancer Therapeutics, Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea. coocoori@amc.seoul.kr.|Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea. coocoori@amc.seoul.kr.
authors.forename: Si Yeol
authors.initials: SY
authors.lastname: Song
authors.affiliation: Center for Development and Commercialization of Anti-cancer Therapeutics, Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea. syj@amc.seoul.kr.|Asan Institute for Life Science, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea. syj@amc.seoul.kr.
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Center for Development and Commercialization of Anti-cancer Therapeutics, Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea. ekchoi@amc.seoul.kr.|Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea. ekchoi@amc.seoul.kr.
authors.forename: Eun Kyung
authors.identifier: http://orcid.org/0000-0002-5265-7640
authors.initials: EK
authors.lastname: Choi
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology / Q000532:radiotherapy; D000077192:Adenocarcinoma of Lung; D000595:Amino Acid Sequence; D000818:Animals; D017104:Bacteriophage M13 / Q000737:chemistry / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D042241:Early Diagnosis; D005456:Fluorescent Dyes / Q000737:chemistry; D005720:Gamma Rays; D064593:Heterografts; D006801:Humans; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015335:Molecular Probes / Q000096:biosynthesis / Q000737:chemistry*; D061848:Optical Imaging; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry*; D019151:Peptide Library
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D015335:Molecular Probes; D010446:Peptide Fragments; D019151:Peptide Library
keywords: Human lung adenocarcinoma; Imaging; In vivo peptide screening