Clinical molecular imaging in intestinal graft-versus-host disease: mapping of disease activity, prediction, and monitoring of treatment efficiency by positron emission tomography.
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 (18)F-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.
Department of Medicine/Hematology and Oncology, University of Muenster, Albert-Schweitzer-Strasse 33, Muenster, Germany.
Matthias
M
Stelljes
Sven
S
Hermann
Jörn
J
Albring
Gabriele
G
Köhler
Markus
M
Löffler
Christiane
C
Franzius
Christopher
C
Poremba
Verena
V
Schlösser
Sarah
S
Volkmann
Corinna
C
Opitz
Christoph
C
Bremer
Torsten
T
Kucharzik
Gerda
G
Silling
Otmar
O
Schober
Wolfgang E
WE
Berdel
Michael
M
Schäfers
Joachim
J
Kienast
D000328:Adult; D000368:Aged; D000818:Animals; D002465:Cell Movement; D003106:Colon / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006086:Graft vs Host Disease / Q000473:pathology* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007249:Inflammation; D007410:Intestinal Diseases / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D051598:Whole Body Imaging
D019788:Fluorodeoxyglucose F18