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

被引:54
作者
Barrera, P
van der Laken, CJ
Boerman, OC
Oyen, WJG
van de Ven, MTP
van Lent, PLEM
van de Putte, LBA
Corstens, FHM
机构
[1] Univ Nijmegen Hosp, Dept Rheumatol, NL-6500 HB Nijmegen, Netherlands
[2] Univ Nijmegen Hosp, Dept Nucl Med, NL-6500 HB Nijmegen, Netherlands
关键词
D O I
10.1093/rheumatology/39.8.870
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:870 / 874
页数:5
相关论文
共 18 条
[1]  
ARNETT FC, 1987, ARTHRITIS RHEUM, V31, P315
[2]   Prevention of murine collagen-induced arthritis in the knee and ipsilateral paw by local expression of human interleukin-1 receptor antagonist protein in the knee [J].
Bakker, AC ;
Joosten, LAB ;
Arntz, OJ ;
Helsen, MMA ;
Bendele, AM ;
vandeLoo, FAJ ;
vandenBerg, WB .
ARTHRITIS AND RHEUMATISM, 1997, 40 (05) :893-900
[3]  
Bresnihan B, 1998, ARTHRITIS RHEUM, V41, P2196, DOI 10.1002/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO
[4]  
2-2
[5]   Dose-range and dose-frequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis [J].
Campion, GV ;
Lebsack, ME ;
Lookabaugh, J ;
Gordon, G ;
Catalano, M ;
Borenstein, D ;
Caldwell, J ;
Cohen, SA ;
Cohen, SB ;
Fleischmann, R ;
Heller, MD ;
Howard, P ;
Jaffer, AM ;
Kaine, JL ;
Kitsis, E ;
Kopp, EJ ;
Moreland, LW ;
OHanlan, M ;
Prupas, M ;
Rosenberg, A ;
Rutstein, J ;
Sack, MR ;
Schiff, MH ;
Singleton, CM ;
Taborn, J ;
Tindall, E ;
Weaver, AL ;
Yocum, D .
ARTHRITIS AND RHEUMATISM, 1996, 39 (07) :1092-1101
[6]   Tc-99(m)-HIG accumulates in the synovial tissue of rats with adjuvant arthritis by binding to extracellular matrix proteins [J].
deBois, MHW ;
Welling, M ;
Verwey, CL ;
deVries, E ;
Pauwels, EKJ ;
Breedveld, FC ;
Tak, PP .
NUCLEAR MEDICINE COMMUNICATIONS, 1996, 17 (01) :54-59
[7]  
DELEURAN BW, 1992, BRIT J RHEUMATOL, V31, P801
[8]   Biologic basis for interleukin-1 in disease [J].
Dinarello, CA .
BLOOD, 1996, 87 (06) :2095-2147
[9]   REPEATED THERAPY WITH MONOCLONAL-ANTIBODY TO TUMOR-NECROSIS-FACTOR-ALPHA (CA2) IN PATIENTS WITH RHEUMATOID-ARTHRITIS [J].
ELLIOTT, MJ ;
MAINI, RN ;
FELDMANN, M ;
LONGFOX, A ;
CHARLES, P ;
BIJL, H ;
WOODY, JN .
LANCET, 1994, 344 (8930) :1125-1127
[10]   Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice - A comparative study using anti-TNF alpha, anti-IL-1 alpha/beta, and IL-1Ra [J].
Joosten, LAB ;
Helsen, MMA ;
vandeLoo, FAJ ;
vandenBerg, WB .
ARTHRITIS AND RHEUMATISM, 1996, 39 (05) :797-809