title: In vivo imaging of reactive oxygen and nitrogen species in murine colitis.
abstract: 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.
authors.affiliation: *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.
authors.forename: M Nadeem
authors.initials: MN
authors.lastname: Asghar
authors.forename: Rohini
authors.initials: R
authors.lastname: Emani
authors.forename: Catharina
authors.initials: C
authors.lastname: Alam
authors.forename: Terhi O
authors.initials: TO
authors.lastname: Helenius
authors.forename: Tove J
authors.initials: TJ
authors.lastname: Grönroos
authors.forename: Outi
authors.initials: O
authors.lastname: Sareila
authors.forename: Mueez U
authors.initials: MU
authors.lastname: Din
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Arno
authors.initials: A
authors.lastname: Hänninen
authors.forename: Diana M
authors.initials: DM
authors.lastname: Toivola
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D005260:Female; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000175:diagnosis* / Q000378:metabolism; D053533:Keratin-8 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D049268:Positron-Emission Tomography; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D053533:Keratin-8; C486595:Krt8 protein, mouse; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D016264:Dextran Sulfate