Rat antigen-induced arthritis: cartilage alterations assessed with iodine-123-antileukoproteinase.
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.
Kinne
R W
RW
Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Germany.
Meyer
P
P
Gründer
W
W
Buchner
E
E
Palombo-Kinne
E
E
Heinzel-Wieland
R
R
Becker
W
W
Wolf
F
F
Kalden
J R
JR
Burkhardt
H
H
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
D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D009211:Myoglobin; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D019275:Radiopharmaceuticals; D015842:Serine Proteinase Inhibitors