Radiolabelled interleukin-1 receptor antagonist for detection of synovitisin patients with rheumatoid arthritis

Objectives. To investigate the distribution of radiolabelled interleukin-1 receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA) and to assess whether this cytokine is suitable for scintigraphic visualizatio n of synovitis. Methods. In patients with active RR, scintigraphy was performed after a sin gle i.v. dose of [I-123]IL-1ra. Clearance and organ distribution of radiola belled IL-1ra were studied. To assess whether radiolabelled IL-1ra targets the synovial IL-1 receptors, the scintigraphic images obtained with IL-1ra were compared with those obtained by the use of a non-specific control agen t. In addition, autoradiography was pel formed in mice with antigen-induced arthritis that were injected with either radiolabelled IL-1ra or a size-ma tched, non-receptor-binding protein. Results. Radiolabelled IL-1ra allowed clear visualization of inflamed joint s. Specificity in the detection of synovitis was high, whereas a number of painful and swollen joints were not visualized by scintigraphy. The procedu re was well tolerated and [I-123]IL-1ra was rapidly cleared from the circul ation (t(1/2)alpha 11 min, t(1/2)beta 612 min) and excreted mainly in the u rine. The definition of synovial contours by IL-1ra scintigraphy was not ba tter than that observed with a non-specific agent. Although radiolabelled I L-1ra retained its affinity for IL-1 receptors, no binding to synovium was observed by autoradiography. Conclusions. Radiolabelled IL-1ra allows the visualization of synovitis in patients with RA. However. neither the imaging nor the autoradiographic stu dies indicate that joint accumulation of radiolabelled IL-1ra is due to spe cific IL-1 receptor targeting. IL-1ra has proved its therapeutic value in R A, but with the dose schedule in this study it does not behave as a specifi c radiopharmaceutical that is suitable for scintigraphic detection of infla mmation.