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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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TRANSPLANTATION

Clinical molecular imaging in intestinal graft-versus-host disease: mapping of disease activity, prediction, and monitoring of treatment efficiency by positron emission tomography

Matthias Stelljes1, Sven Hermann2, Jörn Albring1, Gabriele Köhler3, Markus Löffler2, Christiane Franzius2, Christopher Poremba4, Verena Schlösser1, Sarah Volkmann1, Corinna Opitz1, Christoph Bremer5, Torsten Kucharzik6, Gerda Silling1, Otmar Schober2, Wolfgang E. Berdel1, Michael Schäfers2, and Joachim Kienast1

1 Department of Medicine/Hematology and Oncology, University of Muenster, Muenster; 2 Department of Nuclear Medicine, University of Muenster, Muenster; 3 Institute of Pathology, University of Muenster, Muenster; 4 Department of Pathology, University of Duesseldorf, Duesseldorf; 5 Department of Clinical Radiology, University of Muenster; Muenster; and 6 Department of Medicine B, University of Muenster, Muenster, Germany

Gastrointestinal graft-versus-host disease (GVHD) is a common and potentially life-threatening complication after allogeneic hematopoietic stem-cell transplantation (HSCT). Noninvasive 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 transplantation 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+ 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. A total of 14 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 histologic evidence of intestinal GVHD. Our findings indicate that FDG-PET is a sensitive and specific noninvasive imaging technique to assess intestinal GVHD, map its localization, and 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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