title: Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment.
abstract: 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.
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research &Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577 Japan.|Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, 277-8561 Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Obonai
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research &Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577 Japan.|Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, 277-8561 Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Fuchigami
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research &Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577 Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Furuya
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research &Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577 Japan.|Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, 277-8561 Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kozuka
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research &Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577 Japan.|Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, 277-8561 Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasunaga
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research &Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577 Japan.|Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, 277-8561 Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D055088:Early Detection of Cancer; D005337:Fibrin / Q000276:immunology*; D005818:Genetic Engineering; D006801:Humans; D051379:Mice; D009154:Mutation; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D000911:Antibodies, Monoclonal; D005337:Fibrin