title: Rat antigen-induced arthritis: cartilage alterations assessed with iodine-123-antileukoproteinase.
abstract: Imaging of cartilage alterations was attempted in joints of rats with chronic antigen-induced arthritis (AIA) using the cationic 123I-labeled serine proteinase inhibitor antileukoproteinase (123I-ALP; pI > 10), which selectively accumulates in normal cartilage, presumably through interaction with negatively charged proteoglycans.
  
  
  METHODS
  Iodine-123-ALP or 123I-myoglobin, a control protein of comparable size but with different isoelectric point (pI=7.3) was injected intravenously into normal or AIA rats. Joint accumulation was followed by scintigraphy for 14 hr. Tissue radioactivity was assessed by well-counter measurements after dissection. The content of charged molecules in articular cartilage was determined by toluidine blue staining; the degree of joint destruction was assessed in parallel by x-ray, ex vivo MRI and histopathology.
  
  
  RESULTS
  In intact articular cartilage, ALP accumulated to a significantly higher degree than myoglobin. This preferential accumulation was lost in rats with chronic AIA. The target-to-background ratio for 123I-ALP negatively correlated with the loss of toluidine blue staining in cartilage, which documents depletion of charged matrix molecules (r=-0.92, p < 0.01 at 4 hr; r=-0.97, p < 0.01 at 13 hr). ALP scintigraphy was sensitive in detecting cartilage alterations, even though the degree of joint destruction and inflammatory infiltration was mild, as demonstrated by x-ray, MRI and histopathology.
  
  
  CONCLUSIONS
  In rat AIA, loss of ALP accumulation appears to document proteoglycan depletion in mildly altered arthritic cartilage. ALP scintigraphy may represent a functional assay for early, premorphological cartilage alterations in human arthritis as well.
authors.affiliation: Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Germany.
authors.forename: R W
authors.initials: RW
authors.lastname: Kinne
authors.forename: P
authors.initials: P
authors.lastname: Meyer
authors.forename: W
authors.initials: W
authors.lastname: Gründer
authors.forename: E
authors.initials: E
authors.lastname: Buchner
authors.forename: E
authors.initials: E
authors.lastname: Palombo-Kinne
authors.forename: R
authors.initials: R
authors.lastname: Heinzel-Wieland
authors.forename: W
authors.initials: W
authors.lastname: Becker
authors.forename: F
authors.initials: F
authors.lastname: Wolf
authors.forename: J R
authors.initials: JR
authors.lastname: Kalden
authors.forename: H
authors.initials: H
authors.lastname: Burkhardt
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging*; D002356:Cartilage / Q000000981:diagnostic imaging*; D005260:Female; D006614:Hindlimb; D007457:Iodine Radioisotopes; D007719:Knee Joint / Q000000981:diagnostic imaging; D008565:Membrane Proteins / Q000493:pharmacokinetics; D009211:Myoglobin / Q000493:pharmacokinetics; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D011917:Rats, Inbred Lew; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D009211:Myoglobin; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D019275:Radiopharmaceuticals; D015842:Serine Proteinase Inhibitors