Longitudinal Quantification of Inflammation in the Murine Dextran Sodium Sulfate-induced Colitis Model Using μPET/CT

Background: This study investigates whether deoxy-2-[18F]fluoro-d-glucose (FDG) micro-positron emission tomography (mu PET)/computed tomography (CT) can serve as a tool for monitoring of the commonly used dextran sodium sulfate (DSS)-induced murine model of inflammatory bowel disease (IBD). Methods: DSS-colitis was induced in Sv129 mice. In a first experiment, four animals were serially scanned with CT and FDG-mu PET on days 0, 3, 7, 11, and 14. The ratio of the mean voxel count of the PET images in the colon and the brain was compared with the histological inflammation score and the colonic myeloperoxidase levels. A second experiment was performed to investigate whether FDG-mu PET was able to detect differences in inflammation between two DSS-treated groups, one receiving placebo (n = 4) and one receiving dimethyloxalylglycine (DMOG) (n = 4), a compound that protects against DSS-induced colitis. Results: The progression of the colonic/brain FDG-signal ratio (over days 0-14) agreed with the predicted histological inflammation score, obtained from a parallel DSS-experiment. Moreover, the quantification of normalized colonic FDG-activity at the final timepoint (day 14) showed an excellent correlation with both the MPO levels (Spearman's rho 1) and the histological inflammation score (Spearman's rho = 0.949) of the scanned mice. The protective action of DMOG in DSS colitis was clearly demonstrated with FDG-mu PET/CT (normalized colonic FDG-activity DMOG versus placebo: P < 0.05). Conclusions: FDG-mu PET-CT is a feasible and reliable noninvasive method to monitor murine DSS-induced colitis. The implementation of this technique in this widely used IBD model opens a new window for pathophysiological research and high-throughput screening of potential therapeutic compounds in preclinical IBD research.