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 123 I-labeled serine proteinase inhibitor antileukoproteinase ( 123 I-ALP; pl > 10), which selectively accumulates in normal cartilage, presumably through interaction with negatively charged proteoglycans. Methods: iodine-123-ALP or 123 l-myoglobin, a control protein of comparable size but with different isoelectric point (pl = 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 123 l-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. Conclusion: 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.