Colonoscopy and μPET/CT are valid techniques to monitor inflammation in the adoptive transfer colitis model in mice

Abstract

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 m-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 6 0.6) to week 8 (6.0 6 1.1). In study 3, colitis was detected 2 weeks after transfer by μPET/CT (2.0 6 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. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.