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. 2003 Sep;62(9):825–828. doi: 10.1136/ard.62.9.825

Scintigraphic detection of tumour necrosis factor in patients with rheumatoid arthritis

P Barrera 1, W Oyen 1, O Boerman 1, P L C M van Riel 1
PMCID: PMC1754647  PMID: 12922953

Abstract

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 TNFα 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.

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Figure 1.

Figure 1

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Scintigraphic images of the whole body and hands of a patient with active RA after injection of 99mTc human anti-TNF mAb. (A) The first imaging session. (B) Decreased uptake in joints after administration of an excess unlabelled anti-TNF mAb (hands detail), whereas the uptake in the reticuloendothelial organs remains unchanged (whole body).

Figure 2.

Figure 2

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Course of the DAS during the study. Patients with active RA underwent a first scintigraphy with a tracer dose of a fully human anti-TNF mAb radiolabelled with 99mTc. Two weeks thereafter, a subset of patients (n=5, rhomboids) received a therapeutic dose of the same antibody (grey arrow) before the second imaging session to assess the TNF targeting in the joints. Another patient subset (n=5, squares) was treated with systemic steroids two days before the second scintigraphy (white arrow).

Selected References

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