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Visualizing inflammation activity in rheumatoid arthritis with Tc-99 m Anti-CD4-mAb fragment scintigraphy
Affiliation:1. Department or Nuclear Medicine, University Hospital, Leipzig, Germany;2. Department of Rheumatology, Medical Department II, University of Leipzig, Germany;3. Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Germany;4. Biotectid GmbH, Leipzig, Germany;5. St. Georg Hospital, Department of Rheumatology, Leipzig, Germany;6. Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany;7. LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Germany;8. Institute for Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany;9. Translational Centre for Regenerative Medicine, Leipzig, Germany;1. Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103 Leipzig, Germany;2. Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, Permoserstrasse 15, D-04318 Leipzig, Germany;3. ABX advanced biochemical compounds GmbH, Heinrich-Glaeser-Strasse 10-14, D-01454 Radeberg, Germany;4. Multimodal Image Processing, Central Institute ZEA-2-Electronic Systems, Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany;5. Department of Psychiatry, University of Leipzig, Semmelweisstrasse 10, D-04103 Leipzig, Germany;6. Integrated Research and Treatment Centre (IFB) Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany;1. Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou 325027, China;2. School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;3. State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou, Zhejiang, China
Abstract:PurposeT-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-99 m labelled murine anti-human CD4 IgG1-Fab fragment ([99mTc]-anti-CD4-Fab, [99mTc]-EP1645) in patients with active synovitis due to RA, and to evaluate its potential as a marker of disease activity.MethodsIn 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 24 h after application of 550 ± 150 MBq [99mTc]-anti-CD4-Fab, followed by visual analyses, comparison with clinical data in 68 joints per patient and semiquantitative analysis of hand and wrist joints.ResultsNeither 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.ConclusionScintigraphy with [99mTc]-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 [99mTc]-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.
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