ORIGINAL ARTICLE Colonoscopy and mPET/CT are Valid Techniques to Monitor Inflammation in the Adoptive Transfer Colitis Model in Mice Marthe Heylen, MPharm,* Steven Deleye, MSc, † Joris G. De Man, MSc,* Nathalie E. Ruyssers, MSc, PhD,* Wim Vermeulen, MSc, PhD,* Sigrid Stroobants, MD, PhD, †,‡ Paul A. Pelckmans, MD, PhD,* ,§ Tom G. Moreels, MD, PhD,* ,§ Steven Staelens, MSc, PhD, † and Benedicte Y. De Winter, MD, PhD* 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 (mPET/CT) as monitoring tools in a model for chronic colitis in mice. Methods: Colitis was induced by adoptive transfer of CD4 + CD25 2 CD62L + T cells in immunocompromised severe combined immunodeficient mice. Three study protocols were designed. In study 1, colonoscopy and mPET/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 mPET/CT (study 3). Each study included postmortem evaluation of colonic inflammation (macroscopy, microscopy, and myeloperoxidase activity). Results: In study 1, both colonoscopy and mPET/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 mPET/CT (2.0 6 0.4) but not by colonoscopy, whereas both techniques detected inflammation 4 and 6 weeks after transfer. Colonoscopy correlated with mPET/CT (r ¼ 0.812, 0.884, and 0.781, respectively) and with postmortem analyses in all 3 studies. Conclusions: Adoptive transfer of CD4 + CD25 2 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 mPET/CT. mPET/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. (Inflamm Bowel Dis 2013;19:967–976) Key Words: colonoscopy, mPET/CT, colitis, adoptive transfer model I nflammatory bowel diseases (IBDs), such as Crohn’s disease, are relapsing chronic inflammatory disorders affecting approximately 0.1% of the Western population. 1 Although the etiology of Crohn’s disease remains unknown, it has been suggested that an activation of the mucosal immune system in response to bacterial antigens with consecutive pathological cytokine production plays a key pathogenic role. 2,3 The pathophysiology and the effect of new emerging therapies are being examined extensively in preclinical studies using experimental animal models of IBD. 4 The number of mouse models of intestinal inflammation increased steadily over the past decades and can be divided into 4 different categories: spontaneous models, inducible models, adoptive transfer models, and genetically engineered models. 5,6 The adoptive T-cell transfer model is considered a promis- ing mouse model of IBD to examine the initiation, induction, and regulation of the immunopathology in chronic colitis mediated by T cells. 7 The adoptive transfer of CD4 + CD25 2 CD62L + T cells in severe combined immunodeficient (SCID) mice induces a chronic colitis, sharing many pathological features with human IBD. 8–13 A major handicap in animal models for IBD is the lack of tools to evaluate sequentially the course of inflammation over a longer period of time. A large number of animals are normally needed, as animals have to be killed at different time points to visualize the inflammation and to follow-up disease progression by postmortem analysis. In addition, only indirect inflammatory parameters such as weight loss, stool consistency, or the presence of blood in the feces could be used to assess the state of disease, lacking appropriate validity as no direct indications of inflamma- tion were monitored. 14,15 In clinical practice, colonoscopic evaluation and imaging techniques are of utmost importance for the diagnosis and staging of IBD, 16 but these techniques are only scarcely used in preclin- ical research. The limitation for colonoscopy is the small diameter Received for publication July 16, 2012; Accepted July 30, 2012. From the *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; and § Division of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium. Supported by Legacy Deceunynck (University of Antwerp). The authors have no conflicts of interest to disclose. 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: benedicte.dewinter@ ua.ac.be). Copyright © 2013 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0b013e3182802c7c Published online 12 February 2013. Inflamm Bowel Dis  Volume 19, Number 5, April 2013 www.ibdjournal.org | 967 Copyright © 2013 Crohn’s & Colitis Foundation of America, Inc. 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