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Rheumatology 2002; 41: 53-61
© 2002 British Society for Rheumatology

Original Papers

Scintigraphy using a technetium 99m-labelled anti-E-selectin Fab fragment in rheumatoid arthritis

F. Jamar1, F. A. Houssiau2, J.-P. Devogelaer2, P. T. Chapman3, D. O. Haskard3, V. Beaujean1, C. Beckers1, D.-H. Manicourt1,2 and A. M. Peters4,

1 Centre of Nuclear Medicine and
2 Department of Rheumatology, University of Louvain Medical School, Brussels, Belgium and the
3 National Heart and Lung Institute and
4 Department of Imaging, Imperial College (Hammersmith Campus), London, UK

Objective. We previously described a novel radiolabelled monoclonal antibody (1.2B6), which reacts with porcine E-selectin, for targeting activated endothelium as a means of imaging inflammatory disorders, and presented initial clinical work based on 111In-labelled antibody. The aim of the present study was to evaluate a Fab fragment of 1.2B6 labelled with 99mTc in patients with rheumatoid arthritis (RA) by comparison with (i) 111In-labelled 1.2B6 F(ab')2 and (ii) conventional bone scanning.

Methods. 99mTc-1.2B6-Fab (~440 MBq) and 111In-1.2B6-F(ab')2 (~27 MBq) were compared in 10 patients using a double-isotope protocol. Images were obtained 4 and 20–24 h after injection. Two normal volunteers were also imaged. In a separate group of 16 patients, 99mTc-1.2B6-Fab and 99mTc-oxidronate (99mTc-HDP) (~740 MBq) were compared on the basis of visual and semi-quantitative analysis of joint uptake (joint/soft tissue ratios) 4 h after injection. The respective biodistributions and blood clearances of the two 1.2B6 fragments were also compared.

Results. Image contrast was slightly better with 99mTc-Fab at 4 h but equal for the two tracers at 24 h. Diagnostic accuracy, taking joint tenderness or swelling as the clinical endpoint, was 76% for both fragments at 24 h. Plasma clearance of 99mTc-Fab was faster than that of 111In-F(ab')2 (t1/2 142 vs 421 min; P<0.0001). 99mTc-Fab appeared somewhat unstable in vivo, as shown by activity in the thyroid gland and bowel. The diagnostic accuracy of 99mTc-Fab was 88%, higher than that of 99mTc-HDP (57%) as a result of the low specificity of the latter in RA. Receiver operating characteristic (ROC) curve analysis using joint/soft tissue ratios as a variable cut-off showed that 99mTc-Fab discriminates better than 99mTc-HDP between actively inflamed and silent joints (Z=4.72; P<0.0001). No uptake of 99mTc-Fab was observed by inactive or normal joints, whereas 99mTc-HDP was taken up by all joints to a variable degree, making the decision as to whether a particular joint is actively involved or chronically damaged very difficult.

Conclusion. 99mTc-anti-E-selectin-Fab scintigraphy can be used successfully to image synovitis with better specificity than 99mTc-HDP bone scanning. The advantages over 111In-1.2B6-F(ab')2 are easier availability of the radionuclide, improved physical properties and optimal imaging 4 h after injection.

KEY WORDS: Rheumatoid arthritis, E-selectin, Endothelium, Monoclonal antibody.

Correspondence to: A. M. Peters, Department of Nuclear Medicine, Box 170, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.


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