title: Imaging hamster model of bile duct cancer in vivo using fluorescent L-glucose derivatives.
abstract: Extrahepatic bile duct cancer (cholangiocarcinoma) has a poor prognosis. Since surgical resection is the only way to prolong the patient's life, it is of critical importance to correctly determine the extent of lesions. However, conventional pre-operative assessments have insufficient spatial resolution for determining the surgical margin. A fluorescent contrast agent might provide a more precise measure to identify anomalies in biliary surface, when combined with probe-based confocal laser endomicroscopy (pCLE). We have previously shown that 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-L-glucose (2-NBDLG), a fluorescent derivative of L-glucose (fLG), is specifically taken up into spheroids consisting of cells showing heterogeneous nuclear-cytoplasm ratio, a feature of malignant cells in clinical settings. In addition, a combined use of 2-TRLG, a membrane-impermeable fLG, with 2-NBDLG visualized membrane integrity as well. We therefore explored in the present study the availability of the fLGs in vivo as a contrast agent for pCLE by using a hamster model of cholangiocarcinoma. Extrahepatic cholangiocarcinoma developed in mid common duct in ~20 % of the animals subjected to cholecystoduodenostomy with the ligation at the distal end of the common duct followed by injection of a carcinogen N-nitrosobis(2-oxopropyl)amine. After infusing bile duct with a solution containing 2-NBDLG and 2-TRLG, the lumen was surgically exposed and examined by pCLE. Fluorescence pattern characterized by bright spots and dark clumps was detected in the areas diagnosed with cholangiocarcinoma in later histopathology, whereas no such pattern was detected in control animals. These findings may form a basis for elucidating a potential availability of fLGs in imaging cholangiocarcinoma by pCLE.
authors: Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors: Hiroshi
authors: H
authors: Yokoyama
authors: Department of Physiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan.
authors: Ayako
authors: A
authors: Sasaki
authors: Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors: Tadashi
authors: T
authors: Yoshizawa
authors: Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors: Hiroshi
authors: H
authors: Kijima
authors: Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors: Kenichi
authors: K
authors: Hakamada
authors: Department of Physiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. kyamada@hirosaki-u.ac.jp.
authors: Katsuya
authors: K
authors: Yamada
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives*; D000818:Animals; D001650:Bile Duct Neoplasms / Q000000981:diagnostic imaging* / Q000648:ultrastructure; D001652:Bile Ducts / Q000000981:diagnostic imaging*; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging* / Q000648:ultrastructure; D006224:Cricetinae; D003847:Deoxyglucose / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D019723:Endoscopes; D005260:Female; D005453:Fluorescence; D008647:Mesocricetus; D018613:Microscopy, Confocal
chemical_list: D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose
keywords: Carcinoma; Endoscope; Imaging; L-glucose; Tumor