Literature DB >> 10952741

Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in patients with rheumatoid arthritis.

P Barrera1, C J van der Laken, O C Boerman, W J Oyen, M T van de Ven, P L van Lent, L B van de Putte, F H Corstens.   

Abstract

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 visualization of synovitis.
METHODS: In patients with active RA, scintigraphy was performed after a single i. v. dose of [(123)I]IL-1ra. Clearance and organ distribution of radiolabelled 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 agent. In addition, autoradiography was performed in mice with antigen-induced arthritis that were injected with either radiolabelled IL-1ra or a size-matched, non-receptor-binding protein.
RESULTS: Radiolabelled IL-1ra allowed clear visualization of inflamed joints. Specificity in the detection of synovitis was high, whereas a number of painful and swollen joints were not visualized by scintigraphy. The procedure was well tolerated and [(123)I]IL-1ra was rapidly cleared from the circulation (t(1/2)alpha 11 min, t(1/2)beta 612 min) and excreted mainly in the urine. The definition of synovial contours by IL-1ra scintigraphy was not better than that observed with a non-specific agent. Although radiolabelled IL-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 studies indicate that joint accumulation of radiolabelled IL-1ra is due to specific IL-1 receptor targeting. IL-1ra has proved its therapeutic value in RA, but with the dose schedule in this study it does not behave as a specific radiopharmaceutical that is suitable for scintigraphic detection of inflammation.

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Year:  2000        PMID: 10952741     DOI: 10.1093/rheumatology/39.8.870

Source DB:  PubMed          Journal:  Rheumatology (Oxford)        ISSN: 1462-0324            Impact factor:   7.580


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