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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2909-2918.
Prepublished online as a Blood First Edition Paper on December 5, 2007; DOI 10.1182/blood-2007-10-119164.
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Submitted October 19, 2007
Accepted December 1, 2007
Clinical molecular imaging in intestinal graft-versus-host disease: mapping of disease activity, prediction and monitoring of treatment efficiency by positron emission tomography
Matthias Stelljes, Sven Hermann, Jorn Albring, Gabriele Kohler, Markus Loffler, Christiane Franzius, Christopher Poremba, Verena Schlosser, Sarah Volkmann, Corinna Opitz, Christoph Bremer, Torsten Kucharzik, Gerda Silling, Otmar Schober, Wolfgang E Berdel, Michael Schafers, and Joachim Kienast*
Department of Medicine / Hematology and Oncology, University of Muenster, Muenster, Germany
Department of Nuclear Medicine, University of Muenster, Muenster, Germany
Institute of Pathology, University of Muenster, Muenster, Germany
Department of Pathology, University of Duesseldorf, Duesseldorf, Germany
Department of Clinical Radiology, University of Muenster, Muenster, Germany
Department of Medicine B, University of Muenster, Muenster, Germany
* Corresponding author; email: kienast{at}uni-muenster.de.
Gastrointestinal graft-versus-host disease (GvHD) is a common and potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Non-invasive tests for assessment of GvHD activity are desirable but lacking. In the present study we were able to visualize intestinal GvHD associated inflammation in an allogeneic murine transplant model by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in vivo. A predominant localization of intestinal GvHD to the colon was verified by histology and fluorescence reflectance imaging of enhanced green fluorescent protein (EGFP) expressing donor cells. Colonic infiltration by EGFP positive donor lymphocytes matched increased FDG uptake in PET examinations. These preclinical data were prospectively translated into 30 patients with suspected intestinal GvHD beyond 20 days after transplantation. Fourteen of 17 patients with a diagnostic histology showed significant FDG uptake of the gut, again predominantly in the colon. No increased FDG uptake was detected in 13 patients without histological evidence of intestinal GvHD. Our findings indicate that FDG-PET is a sensitive and specific non-invasive imaging technique to assess intestinal GvHD, map its localization and to predict and monitor treatment responsiveness. Novel targeted tracers for PET may provide new insights into the pathophysiology of GvHD and bear the potential to further improve GvHD diagnosis.

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