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In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis

Asghar, M. Nadeem MPhil/Lic*; Emani, Rohini MSc; Alam, Catharina PhD*; Helenius, Terhi O. MSc*; Grönroos, Tove J. PhD; Sareila, Outi PhD§,‖; Din, Mueez U. MSc*; Holmdahl, Rikard MD, PhD§,‖; Hänninen, Arno MD, PhD; Toivola, Diana M. PhD*,¶

doi: 10.1097/MIB.0000000000000118
Original Basic Research Articles

Background: Traditional techniques analyzing mouse colitis are invasive, laborious, or indirect. Development of in vivo imaging techniques for specific colitis processes would be useful for monitoring disease progression and/or treatment effectiveness. The aim was to evaluate the applicability of the chemiluminescent probe L-012, which detects reactive oxygen and nitrogen species, for in vivo colitis imaging.

Methods: Two genetic colitis mouse models were used; K8 knockout (K8−/−) mice, which develop early colitis and the nonobese diabetic mice, which develop a transient subclinical colitis. Dextran sulphate sodium was used as a chemical colitis model. Mice were anesthetized, injected intraperitoneally with L-012, imaged, and quantified for chemiluminescent signal in the abdominal region using an IVIS camera system.

Results: K8−/− and nonobese diabetic mice showed increased L-012-mediated chemiluminescence from the abdominal region compared with control mice. L-012 signals correlated with the colitis phenotype assessed by histology and myeloperoxidase staining. Although L-012 chemiluminescence enabled detection of dextran sulphate sodium–induced colitis at an earlier time point compared with traditional methods, large mouse-to-mouse variations were noted. In situ and ex vivo L-012 imaging as well as [18F]FDG-PET imaging of K8−/− mice confirmed that the in vivo signals originated from the distal colon. L-012 in vivo imaging showed a wide variation in reactive oxygen and nitrogen species in young mice, irrespective of K8 genotype. In aging mice L-012 signals were consistently higher in K8−/− as compared to K8+/+ mice.

Conclusions: In vivo imaging using L-012 is a useful, simple, and cost-effective tool to study the level and longitudinal progression of genetic and possibly chemical murine colitis.

Article first published online 30 June 2014.

*Department of Biosciences, Cell Biology, Åbo Akademi University, Biocity, Turku, Finland;

Department of Medical Microbiology and Immunology, and

Turku PET Center, Medicity Research Laboratory, University of Turku, Turku, Finland;

§Medical Inflammation Research, MBB, Karolinska Institutet, Stockholm, Sweden;

Medicity Research Laboratory, University of Turku, Turku, Finland; and

Turku Center for Disease modeling, Turku, Finland.

Reprints: Diana M. Toivola, PhD, Department of Biosciences, Cell biology, Åbo Akademi University, Biocity, Tykistökatu 6A, FI-20520 Turku, Finland (e-mail:

Supported by funding from the Academy of Finland (R.H., A.H., D.M.T.). Sigrid Juselius Foundation (O.S., R.H., D.M.T.), Turku Doctoral Program for Biomedical Sciences (M.N.A.), FP7 IRG (D.T.), ÅAU Center of Excellence (D.T.), Finnish Diabetes Research Foundation (A.H., D.T.) and Päivikki, Sakari Sohlberg Foundation (A.H.), Victoriastiftelsen (T.H.), the Swedish Research Council, and the EU FP7 project Neurinox (R.H.).

The authors have no conflicts of interest to disclose.

Received April 17, 2014

Accepted May 16, 2014

© Crohn's & Colitis Foundation of America, Inc.
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