K Steinhoff1, M Pierer2, J Siegert3, U Pigla4, R Laub4, S Hesse5, W Seidel6, D Sorger5, A Seese5, J U Kuenstler7, H J Pietzsch8, T Lincke5, M Rullmann9, F Emmrich10, O Sabri5. 1. Department or Nuclear Medicine, University Hospital, Leipzig, Germany. Electronic address: KarenGeva.Steinhoff@medizin.uni-leipzig.de. 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. Department or Nuclear Medicine, University Hospital, Leipzig, Germany. 6. St. Georg Hospital, Department of Rheumatology, Leipzig, Germany. 7. Biotectid GmbH, Leipzig, Germany; Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. 8. Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. 9. LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Germany. 10. Institute for Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany; Translational Centre for Regenerative Medicine, Leipzig, Germany.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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-humanCD4 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. CONCLUSION: 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: Amanda C Freise; Kirstin A Zettlitz; Felix B Salazar; Xiang Lu; Richard Tavaré; Anna M Wu Journal: Mol Imaging Biol Date: 2017-08 Impact factor: 3.488
Authors: Pim P van de Donk; Laura Kist de Ruijter; Marjolijn N Lub-de Hooge; Adrienne H Brouwers; Anthonie J van der Wekken; Sjoukje F Oosting; Rudolf Sn Fehrmann; Derk Jan A de Groot; Elisabeth Ge de Vries Journal: Theranostics Date: 2020-01-01 Impact factor: 11.556
Authors: Bjoern Traenkle; Philipp D Kaiser; Stefania Pezzana; Jennifer Richardson; Marius Gramlich; Teresa R Wagner; Dominik Seyfried; Melissa Weldle; Stefanie Holz; Yana Parfyonova; Stefan Nueske; Armin M Scholz; Anne Zeck; Meike Jakobi; Nicole Schneiderhan-Marra; Martin Schaller; Andreas Maurer; Cécile Gouttefangeas; Manfred Kneilling; Bernd J Pichler; Dominik Sonanini; Ulrich Rothbauer Journal: Front Immunol Date: 2021-12-09 Impact factor: 7.561