Gut and Liver 2010; 4(4): 488-497 https://doi.org/10.5009/gnl.2010.4.4.488 Near-Infrared Fluorescence Imaging Using a Protease-Specific Probe for the Detection of Colon Tumors
Author Information
Soon Man Yoon*, Seung-Jae Myung†,‡, Byong Duk Ye†,‡, In-Wha Kim, Nam Gon Lee, Yeon Mi Ryu, Kyeongsoon Park§, Kwangmeyung Kim§, Ick Chan Kwon§, Young Soo Park, Chan-Sik Park, Dae Hyuk Moon‡,¶, Do Hoon Kim, Mi Young Do, Jeong-Sik Byeon, Suk-Kyun Yang, and Jin-Ho Kim
*Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Department of Internal Medicine and Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, Molecular Imaging Center, Asan Institute for Life Sciences, §Biomedical Research Center, Korea Institute of Science and Technology, Departments of Pathology and Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Seung-Jae Myung
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

Abstract
Background/Aims: Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages. Methods: We utilized two murine colon cancer models: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe. Results: Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa. Conclusions: NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease. (Gut Liver 2010;4:488-497)
Keywords: Colon cancer; Inflammatory bowel disease; Near-infrared fluorescence; Matrix metalloproteinases
Abstract
Background/Aims: Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages. Methods: We utilized two murine colon cancer models: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe. Results: Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa. Conclusions: NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease. (Gut Liver 2010;4:488-497)
Keywords: Colon cancer; Inflammatory bowel disease; Near-infrared fluorescence; Matrix metalloproteinases
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