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

Abstract

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.