In vivo imaging of reactive oxygen and nitrogen species in murine colitis

• Published in: Inflammatory bowel diseases Vol. 20; no. 8; pp. 1435 - 1447
• Main Authors: Asghar, M Nadeem, Emani, Rohini, Alam, Catharina, Helenius, Terhi O, Grönroos, Tove J, Sareila, Outi, Din, Mueez U, Holmdahl, Rikard, Hänninen, Arno, Toivola, Diana M
• Format: Journal Article
• Language: English
• Published: England 01-08-2014
• Subjects: Animals; Colitis - chemically induced; Colitis - complications; Colitis - metabolism; Colitis - pathology; Dextran Sulfate - toxicity; Diagnostic Imaging; Disease Models, Animal; Female; Image Processing, Computer-Assisted; Inflammation - diagnosis; Inflammation - metabolism; Keratin-8 - genetics; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mice, Knockout; Positron-Emission Tomography; Reactive Nitrogen Species - metabolism; Reactive Oxygen Species - metabolism
• ISSN: 1078-0998; 1536-4844; 1536-4844
• DOI: 10.1097/mib.0000000000000118

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.
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.
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.
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.