title: Assessment of rat antigen-induced arthritis and its suppression during glucocorticoid therapy by use of hemicyanine dye probes with different molecular weight in near-infrared fluorescence optical imaging.
abstract: OBJECTIVE
  Arthritic joints are ideal disease entities to be assessed via optical imaging. Here, we investigated the selective accumulation behavior of two differently sized hemicyanine optical probes in arthritic joints and its modification during glucocorticoid therapy in the course of inflammation.
  
  
  METHODS
  The well-standardized preclinical antigen-induced arthritis (AIA) model in rats was used. The animals were divided into 3 groups: arthritic, arthritic and dexamethasone-treated, and immunized only. After intravenous coinjection of DY-752 (size, 800 Da) and DY-682-(rat) IgG (size, 150 kDa) probes, spectrally unmixed near-infrared fluorescence images were acquired and analyzed semiquantitatively. Probe organ distribution, joint swelling, blood cell counts, joint vessel density, and histological scoring of arthritis were determined.
  
  
  RESULTS
  The local joint accumulation kinetics of the DY-752 probe differed from the DY-682-IgG one. In the course of AIA, probe signaling in arthritic joints was similar between each other. Joint swelling and histological scoring were in accordance with signaling. Dexamethasone treatment of rats with AIA significantly reduced both the near-infrared fluorescence signals and severity of arthritis but did not change the joint vascular density or the uptake of the probes by phagocytes. A differential biodistribution of both probes was encountered, but such an accumulation was prevented by dexamethasone treatment.
  
  
  CONCLUSIONS
  Near-infrared fluorescence signaling in the course of AIA closely reflects the pathophysiological events of the arthritic joint and the effects of therapy independently of the molecular size of the probe. The results show the suitability of our hemicyanine probes for imaging of arthritis.
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany.
authors.forename: Frederic
authors.initials: F
authors.lastname: Dietzel
authors.forename: Michael Karl
authors.initials: MK
authors.lastname: Boettger
authors.forename: Katja
authors.initials: K
authors.lastname: Dahlke
authors.forename: Jana
authors.initials: J
authors.lastname: Hölzer
authors.forename: Frank
authors.initials: F
authors.lastname: Lehmann
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
authors.forename: Werner Alois
authors.initials: WA
authors.lastname: Kaiser
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
mesh_terms: D000818:Animals; D000941:Antigens; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D002232:Carbocyanines / Q000737:chemistry*; D003287:Contrast Media; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008856:Microscopy, Fluorescence / Q000379:methods*; D008970:Molecular Weight; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000941:Antigens; D002232:Carbocyanines; D003287:Contrast Media; D007166:Immunosuppressive Agents; D003907:Dexamethasone