Application of peptide displaying phage as a novel diagnostic probe for human lung adenocarcinoma

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• 作者：Kyoung Jin Lee ; Jae Hee Lee ; Hye Kyung Chung ; Eun Jin Ju ; Si Yeol Song…
• 关键词：Human lung adenocarcinoma ; In vivo peptide screening ; Imaging
• 刊名：Amino Acids
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：48
• 期：4
• 页码：1079-1086
• 全文大小：1,921 KB
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• 作者单位：Kyoung Jin Lee (1) (2)
  Jae Hee Lee (1) (2)
  Hye Kyung Chung (3)
  Eun Jin Ju (1) (2)
  Si Yeol Song (1) (4)
  Seong-Yun Jeong (1) (2)
  Eun Kyung Choi (1) (4)
  
  1. 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
  2. Asan Institute for Life Science, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea
  3. Korea Institute of Radiological and Medical Sciences, National Project to Establish Platform To Develop the New Concept Therapy, Seoul, 138-706, Korea
  4. Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199

文摘

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 × 109 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.