Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in patients with rheumatoid arthritis
Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in patients with rheumatoid arthritis
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DOI：
10.1093/rheumatology/39.8.870
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发表时间：
2000-08-01
期刊：
影响因子：
5.5
通讯作者：
Corstens, FHM
中科院分区：
文献类型：
--
作者：
Barrera, P;van der Laken, CJ;Corstens, FHM
目标。目的探讨放射性标记的白细胞介素1受体拮抗剂(IL-1ra)在类风湿关节炎(RA)患者体内的分布情况，并评价该细胞因子是否适用于滑膜炎的核素显像。对于活动性RR的患者，在单次静脉注射后进行核素扫描。[I-123]IL-1ra剂量。对放射性标记的IL-1ra的清除和器官分布进行了研究。为了评估放射性标记的IL-1ra是否针对滑膜IL-1受体，用IL-1ra获得的闪烁图像与使用非特异性控制剂获得的图像进行了比较。此外，在抗原诱导性关节炎的小鼠中，注射了放射性标记的IL-1ra或大小匹配的非受体结合蛋白，形成了放射自显影。放射性标记的IL-1ra可以清楚地显示发炎的关节。诊断滑膜炎的特异度很高，而核素扫描不能显示大量疼痛和肿胀的关节。该过程耐受性良好，[I-123]IL-1ra迅速从循环中清除(t(1/2)α11min，t(1/2)β612min)，并主要在尿液中排泄。IL-1ra核素扫描对滑膜轮廓的清晰度并不比非特异性试剂好。虽然放射性标记的IL-1ra与IL-1受体保持了亲和力，但放射自显影未观察到与滑膜的结合。放射性标记的IL-1ra可用于RA患者滑膜炎的可视化。然而。无论是影像还是放射自显影研究都没有表明放射性标记的IL-1ra的联合聚集是由于特定的IL-1受体靶向。IL-1ra已经证明了其在RA中的治疗价值，但根据本研究中的剂量方案，它并不是一种适合于放射性核素检测炎症的特异性放射性药物。
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 RR, scintigraphy was performed after a single i.v. dose of [I-123]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 pel formed 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 [I-123]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 batter 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.