4.7 Article

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Journal

SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/srep23613

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Funding

  1. National Cancer Center Research and Development Fund [26-A-14, 26-A-12]
  2. Third Term Comprehensive Control Research for Cancer from the Ministry of Health, Labour, and Welfare of Japan
  3. Ministry of Education, Culture, Sports, Science and Technology
  4. Princess Takamatsu Cancer Research Fund
  5. Japanese Foundation for Multidisciplinary Treatment of Cancer
  6. Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and development, AMED [15ck0106114 h0002]
  7. Grants-in-Aid for Scientific Research [15H04316] Funding Source: KAKEN

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The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma.

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