List of selected 3R Methods (ordered according to topics)

Experimental colitis through serial assessment of disease activity by 18F-FDG PET/CT

December 2012

Author: Dominik Bettenworth
Medizinische Klinik und Poliklinik B, Universitätsklinikum Münster
48149 Münster, Germany
Email: dominik.bettenworth@ukmuenster.de

Preclinical evaluation of potential drug candidates for human inflammatory bowel disease is performed in murine models of colitis. The most widely used model is dextran-sodium sulfate(DSS)-induced colitis. Non-invasive imaging of murine experimental colitis by Positron emission tomography (PET) combined with radiotracers is feasible and offers the opportunity of serial follow-up investigations. This technique significantly reduces the number of test animals.

Keywords: gastroenterology; non-invasive imaging; reduction

Method
A valid assessment of dextran-sodium sulfate(DSS)-induced colitis in mice requires histological examinations ex vivo at defined time points, which determines the end of the trial for individual animals. Since endoscopic examinations of mice are challenging and associated with severe stress for the animals, non-invasive imaging was applied, which allows longitudinal, intraindividual follow-up examinations of animals.
It was earlier shown that FDG (fluorodeoxyglucose) uptake correlates well with the degree of mucosal inflammation during the course of disease (Brewer et al. 2008). Hindryckx et al. (2011) investigated longitudinal quantification of inflammation in wild-type mice in murine DSS-induced colitis by FDG-µPET/CT, which is the most widely-used method. The alleviation of induced colitis could be quantified without sacrificing the test animals.
Using FDG-µPET/CT, we found in our own investigations that segmental assessment of colonic inflammation over the course of disease correlated well with histological damage. In addition, we could detect extraintestinal inflammatory changes of bone marrow (Figure 1, arrow), reflecting a systemic immune response. Moreover, we found a strong correlation between mucosal FDG uptake and T-cell infiltration of the colonic wall, indicating that cellular inflammatory infiltrate of the colonic wall can be studied by non-invasive imaging modalities such as 18-FDG PET/CT (Bettenworth 2011).

3R effect
Non-invasive imaging of murine experimental colitis by 18-FDG-PET/CT is feasible and offers the opportunity of serial follow-up investigations to pursue the course of colitis and detect extraintestinal inflammatory changes. Therefore, this technique might significantly reduce the number of required test animals.

References/ Links
1. Brewer S. et al. (2008), Molecular Imaging of Murine Intestinal Inflammation With 2-Deoxy-2-[18F]Fluoro-d-Glucose and Positron Emission Tomography: Gastroenterology 135 / 3: 744-55.

2. Hindryckx P. et al. (2011) Longitudinal quantification of inflammation in the murine dextran sodium sulfate-induced colitis model using μPET/CT, Inflammatory bowel disease 2011;17 / 10: 2058-64.

3. Bettenworth D. et al. (2011) Disease Activity Assessment of Murine DSS-Colitis by 18F-FDG-PET/CT, Gastroenterology 140 / 5: Supplement 1, Page S-424, Su1185 (Abstract).

Figures
Figure 1
3D reconstruction of 18F-FDG PET/CT after initiation of DSS-induced colitis.

Figure 1