Background: Preclinical in vivo research on inflammatory bowel diseases requires proper animal models and techniques allowing longitudinal monitoring of colonic inflammation without the need to kill animals. We evaluated colonoscopy and μ-positron emission tomography/computed tomography (μPET/CT) as monitoring tools in a model for chronic colitis in mice.
Methods: Colitis was induced by adoptive transfer of CD4+CD25−CD62L+ T cells in immunocompromised severe combined immunodeficient mice. Three study protocols were designed. In study 1, colonoscopy and µPET/CT were performed once, 4 weeks after transfer. In study 2 and study 3, colitis was sequentially followed up through colonoscopy (study 2) or colonoscopy plus µPET/CT (study 3). Each study included postmortem evaluation of colonic inflammation (macroscopy, microscopy, and myeloperoxidase activity).
Results: In study 1, both colonoscopy and µPET/CT detected colitis 4 weeks after transfer. Study 2 showed a gradual increase in colonoscopic score from week 2 (1.4 ± 0.6) to week 8 (6.0 ± 1.1). In study 3, colitis was detected 2 weeks after transfer by µPET/CT (2.0 ± 0.4) but not by colonoscopy, whereas both techniques detected inflammation 4 and 6 weeks after transfer. Colonoscopy correlated with µPET/CT (r = 0.812, 0.884, and 0.781, respectively) and with postmortem analyses in all 3 studies.
Conclusions: Adoptive transfer of CD4+CD25−CD62L+ T cells in severe combined immunodeficient mice results in a moderate chronic colitis. Evolution of colitis could be monitored over time by both colonoscopy and µPET/CT. µPET/CT seems to detect inflammation at an earlier time point than colonoscopy. Both techniques represent reliable and safe methods without the need to kill animals.
Article first published online 12 February 2013
*Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology; and
†Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium
‡Division of Nuclear Medicine, Antwerp University Hospital, Antwerp, Belgium
§Division of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
Reprints: Benedicte Y. De Winter, MD, PhD, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Universiteitsplein 1, D.T.2.26, B-2610 Antwerp, Belgium (e-mail: firstname.lastname@example.org).
Supported by Legacy Deceunynck (University of Antwerp).
The authors have no conflicts of interest to disclose.
Received July 16, 2012
Accepted July 30, 2012