Anne Beltzer1, Thomas Kaulisch1, Teresa Bluhmki1, Tanja Schoenberger2, Birgit Stierstorfer2, Detlef Stiller3. 1. Div. Research Germany-Target Discovery Research, In-Vivo Imaging Laboratory, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397, Biberach an der Riß, Germany. 2. Target Discovery Research, Target Validation Technologies, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany. 3. Div. Research Germany-Target Discovery Research, In-Vivo Imaging Laboratory, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397, Biberach an der Riß, Germany. detlef.stiller@boehringer-ingelheim.com.
Abstract
PURPOSE: In humans, colonoscopy is the gold standard for the diagnosis of inflammatory changes of the colon wall. Aim of this study was the identification of less invasive imaging biomarkers in the dextran sodium sulfate (DSS) colitis model to provide additional information on transmural changes of the colon wall. PROCEDURES: Colitis was induced in C57BL/6 mice by administration of 2, 3, and 4 % DSS over a period of 5 days. Colon wall thickness was measured using magnetic resonance imaging (MRI), ultrasound (US), and x-ray computed tomography (CT), gut inflammation by positron emission tomography/CT, and mucosal changes of the colon wall by colonoscopy. Colon samples were examined histologically. RESULTS: MRI, CT, US, and histological data revealed increased colon wall thickness in DSS-treated mice compared to healthy controls. Elevated 2-deoxy-2[(18)F]fluoro-D-glucose uptake and colonoscopy confirmed high inflammatory load in the guts of colitis mice. CONCLUSIONS: The established quantitative imaging readouts offer promising perspectives to develop new compounds and to translate these methods into the clinical setting.
PURPOSE: In humans, colonoscopy is the gold standard for the diagnosis of inflammatory changes of the colon wall. Aim of this study was the identification of less invasive imaging biomarkers in the dextran sodium sulfate (DSS) colitis model to provide additional information on transmural changes of the colon wall. PROCEDURES: Colitis was induced in C57BL/6 mice by administration of 2, 3, and 4 % DSS over a period of 5 days. Colon wall thickness was measured using magnetic resonance imaging (MRI), ultrasound (US), and x-ray computed tomography (CT), gut inflammation by positron emission tomography/CT, and mucosal changes of the colon wall by colonoscopy. Colon samples were examined histologically. RESULTS: MRI, CT, US, and histological data revealed increased colon wall thickness in DSS-treated mice compared to healthy controls. Elevated 2-deoxy-2[(18)F]fluoro-D-glucose uptake and colonoscopy confirmed high inflammatory load in the guts of colitismice. CONCLUSIONS: The established quantitative imaging readouts offer promising perspectives to develop new compounds and to translate these methods into the clinical setting.
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