• Katrin Schwegmann, Dominik Bettenworth, Sven Hermann, Andreas Faust, Christopher Poremba, Dirk Foell, Michael Schäfers, Dirk Domagk, and Philipp Lenz.
• *European Institute for Molecular Imaging, University of Münster, Münster, Germany; †Department of Medicine B, University Hospital Münster, Germany; ‡Institute of Pathology Munich-North, Munich, Germany; §Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Germany; and ‖Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), University of Münster, Münster, Germany.
• Inflamm. Bowel Dis. 2016 Jan 1; 22 (1): 82-91.

BackgroundPatients with ulcerative colitis are at increased risk for colorectal cancer and endoscopic surveillance is mandatory. Matrix metalloproteinases (MMPs)-2 and -9 activities are increased in malignant colonic mucosa. The aim of the study was to evaluate molecular imaging of MMP-2/-9 by fluorescence endoscopy (FE) for early tumor detection.MethodsColorectal cancer in mice (n = 28) was induced by azoxymethane and dextran sodium sulfate. Twenty-four hours after intravenous injection of a nonpeptidic, Cy5.5-labeled MMP-selective tracer, tumor development was assessed in vivo by white light endoscopy and FE. Topical administration of the tracer was also investigated (after 5 minutes and 24 hours). Colonic tumors were evaluated ex vivo by fluorescence reflectance imaging, immunohistochemistry, Western blot analysis, and zymography.ResultsImaging of MMP-2/-9 expression by FE achieved a significantly higher contrast of the fluorescence signal in colonic adenomas compared with the adjacent nonmalignant mucosa (P < 0.001). Fluorescence reflectance imaging detected a significantly higher tracer uptake in adenoma compared with healthy mucosa (P < 0.001) and revealed a tumor size-dependent increase of tracer uptake (P < 0.01). Topical tracer administration did not facilitate tumor detection. Immunohistochemistry, Western blot analysis, and zymography indicated higher levels of MMP-2 and -9 in high-grade dysplasia and pT1 tumors ex vivo.ConclusionsMMP-2/-9 expression was significantly increased in colorectal neoplasia. FE allows direct visualization of a prognostic parameter (here MMP-2/-9) on a molecular level and may improve the characterization of colorectal lesions and the adenoma detection rate in the future.

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