title: Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Departments of Rheumatology and. Nuclear Medicine, University Hospital, Nijmegen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Barrera
authors.forename: C J
authors.initials: CJ
authors.lastname: van der Laken
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: M T
authors.initials: MT
authors.lastname: van de Ven
authors.forename: P L
authors.initials: PL
authors.lastname: van Lent
authors.forename: L B
authors.initials: LB
authors.lastname: van de Putte
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000276:immunology; D001345:Autoradiography; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011877:Radionuclide Imaging; D012710:Serum Albumin, Bovine / Q000276:immunology; D012795:Sialoglycoproteins / Q000493:pharmacokinetics; D013585:Synovitis / Q000000981:diagnostic imaging*
chemical_list: D018501:Antirheumatic Agents; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007457:Iodine Radioisotopes; D012795:Sialoglycoproteins; D012710:Serum Albumin, Bovine