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Scintigraphic detection of tumour necrosis factor in patients with rheumatoid arthritis

P Barrera¹, W J G Oyen², O C Boerman², P L C M van Riel¹

¹ Department of Rheumatology, University Medical Centre, Nijmegen, The Netherlands
² Department of Nuclear Medicine, University Medical Centre, Nijmegen, The Netherlands

Correspondence to:
Correspondence to:
Dr P Barrera, Department of Rheumatology, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands;
p.barrera{at}reuma.azn.nl

Objectives: To investigate the biodistribution and specific targeting for tumour necrosis factor (TNF) of a fully human, radiolabelled anti-TNF monoclonal antibody (anti-TNF mAb) in patients with active rheumatoid arthritis (RA). To assess whether this agent is suitable for visualisation of synovitis.

Methods: Ten patients with RA underwent whole body scintigraphy after administration of a tracer—subtherapeutic dose of 100 µg ^99mTc human anti-TNF mAb. After two weeks, the procedure was repeated to assess the specificity of the radiolabelled antibody for TNF and its sensitivity for changes in inflammation. Therefore, a competition study was performed in five patients, who received excess unlabelled anti-TNF mAb before the tracer dose of ^99mTc-anti-TNF. Another five patients received 120 mg methylprednisolone two days before the second scintigraphy.

Results: Radiolabelled anti-TNF mAb allowed clear visualisation of inflamed joints in patients with active RA with a high specificity. Concomitant administration of excess unlabelled anti-TNF reduced the joint uptake of ^99mTc-anti-TNF mAb by a median of 25% as a percentage of the injected dose after 24 hours, whereas uptake in liver and spleen remained unchanged. Systemic corticosteroids reduced the disease activity, which was mirrored by a decreased joint uptake of the tracer. The anti-TNF mAb retained its high affinity for TNF after labelling and was cleared from the circulation with an elimination half life of 48 hours. The procedure was well tolerated.

Conclusions: Radiolabelled human anti-TNF mAb allows visualisation of synovitis in patients with RA. Joint accumulation of this agent is partly due to specific TNF targeting and is highly predictive for inflammation.

Keywords: monoclonal antibodies; rheumatoid arthritis; scintigraphy; tumour necrosis factor

Abbreviations: DAS, disease activity score; HPLC, high performance liquid chromatography; HYNIC, hydrazinicotinamide; ID, injected dose; mAb, monoclonal antibody; RA, rheumatoid arthritis; TNF, tumour necrosis factor

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