title: Visualizing inflammation activity in rheumatoid arthritis with Tc-99 m anti-CD4-mAb fragment scintigraphy.
abstract: OBJECTIVE
  T-cell-located CD4 antigen represents one of the therapeutic targets in rheumatoid arthritis (RA). However, up to now there is no established imaging tool to visualize this target in vivo. The aim of our study was to assess the safety and tolerability of a technetium-99m labelled murine anti-human CD4 IgG1-Fab fragment ([(99m)Tc]-anti-CD4-Fab, [(99m)Tc]-EP1645) in patients with active synovitis due to RA, and to evaluate its potential as a marker of disease activity.
  
  
  METHODS
  In the present phase I proof of principle study five patients with RA were examined. Planar scans of the whole body, hands, and feet were taken 30 min up to 24h after application of 550 ± 150 MBq [(99m)Tc]-anti-CD4-Fab, followed by visual analyses, comparison with clinical data in 68 joints per patient and semiquantitative analysis of hand and wrist joints.
  
  
  RESULTS
  Neither infusion related adverse events nor adverse events during follow up were observed. No increase in human anti-murine antibody titres was seen. All patients had positive scans in almost 70% of clinically affected joints. Positive scans were also found in 8% of joints without evidence of swelling or tenderness.
  
  
  CONCLUSIONS
  Scintigraphy with [(99m)Tc]-anti-CD4-Fab is a promising technique for evaluation of inflammatory activity in patients with RA, pre-therapeutical evaluation of CD4 status and therapy control. Tracer uptake in clinically inconspicuous joints strongly indicates diagnostic potential of [(99m)Tc]-anti-CD4-Fab. Whether this technique is eligible as a prognostic factor in RA needs to be analysed in further studies as well as the pathophysiological background of clinically affected joints lacking tracer uptake.
authors: Department or Nuclear Medicine, University Hospital, Leipzig, Germany. Electronic address: KarenGeva.Steinhoff@medizin.uni-leipzig.de.
authors: K
authors: K
authors: Steinhoff
authors: Department of Rheumatology, Medical Department II, University of Leipzig, Germany.
authors: M
authors: M
authors: Pierer
authors: Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Germany.
authors: J
authors: J
authors: Siegert
authors: Biotectid GmbH, Leipzig, Germany.
authors: U
authors: U
authors: Pigla
authors: Biotectid GmbH, Leipzig, Germany.
authors: R
authors: R
authors: Laub
authors: Department or Nuclear Medicine, University Hospital, Leipzig, Germany.
authors: S
authors: S
authors: Hesse
authors: St. Georg Hospital, Department of Rheumatology, Leipzig, Germany.
authors: W
authors: W
authors: Seidel
authors: Department or Nuclear Medicine, University Hospital, Leipzig, Germany.
authors: D
authors: D
authors: Sorger
authors: Department or Nuclear Medicine, University Hospital, Leipzig, Germany.
authors: A
authors: A
authors: Seese
authors: Biotectid GmbH, Leipzig, Germany; Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
authors: J U
authors: JU
authors: Kuenstler
authors: Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
authors: H J
authors: HJ
authors: Pietzsch
authors: Department or Nuclear Medicine, University Hospital, Leipzig, Germany.
authors: T
authors: T
authors: Lincke
authors: LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Germany.
authors: M
authors: M
authors: Rullmann
authors: Institute for Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany; Translational Centre for Regenerative Medicine, Leipzig, Germany.
authors: F
authors: F
authors: Emmrich
authors: Department or Nuclear Medicine, University Hospital, Leipzig, Germany.
authors: O
authors: O
authors: Sabri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging*; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D012449:Safety; D013667:Technetium
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D013667:Technetium
keywords: CD4; Molecular imaging; Monoclonal antibodies; Rheumatoid arthritis; Technetium-99m scintigraphy