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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-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. 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 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. 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 [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.

T‐cell‐located CD4 antigen represents one of the therapeutic targets in rheumatoid arthritis (RA). However, up to now it has not been possible to visualize this target in vivo. The aim of our study was to assess the safety and tolerability of a Technetium 99 labelled anti‐CD4 antibody fragment (Tc‐99m‐anti‐CD4) in patients with active synovitis due to rheumatoid arthritis and to evaluate its potential as a marker of disease activity. Methods: In the present phase I proof of principle study 5 patients (3 female, 2 male, 58 to 71 years) with RA were examined. Planar whole body scans as well as separate hand and feet scintigraphies were taken 30 minutes, 1, 2, 4, 8 and 24 hours after application of 585 +/‐ 115 MBq Tc‐99m‐anti‐CD4. The obtained scintigramms were analysed visually and compared with clinical data in 68 joints per patient. Active inflammation was clinically defined by swelling and tenderness in at least one joint (gold standard). Patients were clinically re‐evaluated 7 days p.i. Results: Neither infusion related adverse events nor adverse events during follow up were observed. No increase in HAMA titres was seen. All 5 patients had positive scans in 25 of 37 clinically affected joints. Positive scans were also found in 19 out of 227 joints without evidence of swelling or tenderness yielding a 7% rate of false positive joints and a 32% rate of false negative joints. Conclusion: Scintigraphy with Tc‐99m‐anti‐CD4 is a new promising technique for evaluation of inflammatory activity in patients with RA. Tracer uptake in clinically inconspicuous joints strongly indicates diagnostic potential of 99Tc anti CD4. Based on the few patients investigated, it seems that inflammation is detected with apparently higher specificity than sensitivity. Whether this technique is eligible for prognostic disease evaluation needs to be analysed in further studies as well as the pathophysiological background of clinically affected joints lacking tracer uptake.

Ziel/Aim: Das auf T-Zellen lokalisierte Antigen CD4 stellt ein therapeutisches Target der Therapie der rheumatischen Arthritis dar. Bisher konnte diese Zielstruktur bildgebend jedoch nicht dargestellt werden. Ziel dieser Pilotstudie war es, die Verträglichkeit und Verteilung eines neuen murinen Tc-markierten Anti-CD4-Antikörperfragmentes bei Patienten mit rheumatischer Arthritis und dessen Eignung als Aktivitätsmarker einzuschätzen. Methodik/Methods: In die Studie wurden 3 weibliche und 2 männliche Patienten im Alter von 58 bis 71Jahren untersucht. Jeweils 30min, 1, 2, 4, 8 und 24 Stunden nach i.v. Applikation von 585 +/- 115 MBq wurden planare Ganz- und Teilkörper-Szintigraphien angefertigt und visuell in jeweils 68 Gelenken ausgewertet. Eine aktive Entzündung wurde klinisch durch Schwellung und Schmerz in mindestens einem Gelenk definiert (Gold-Standard). Die Patienten wurden bis 7 Tage p.i. klinisch nachuntersucht. Ergebnisse/Results: Nebenwirkungen konnten weder akut noch im weiteren Verlauf beobachtet werden. Ein Anstieg des humanen Anti-Murinen-Antikörper-Titers wurde ebenfalls nicht verzeichnet. Bei allen 5 Patienten zeigten sich szintigraphisch positive Befunde in 25 von 37 klinisch mit Schmerz und Schwellung betroffenen Gelenken. Szintigraphisch positiv waren 19 von 277 Gelenken ohne klinisch nachweisbare Schmerz oder Schwellung. Somit errechnet sich eine Rate falsch-positiver Befunde von 7% und falsch-negativer Befunde von 32%. Schlussfolgerungen/Conclusions: Die Tc-99m-Anti-CD4-mAb-Fragment-Szintigraphie ist eine vielversprechende neue Technik zur Evaluierung der Lymphozytenaktivität im chronischen und akuten Stadium einer rheumatischen Arthritis, wobei offenbar die Spezifität höher ist als die Sensitivität. Ob damit auch eine Prognoseabschätzung möglich ist, müssen die Folgestudien mit längerem Follow-Up zeigen.