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 (111)In-labelled antibody. The aim of the present study was to evaluate a Fab fragment of 1.2B6 labelled with (99m)Tc in patients with rheumatoid arthritis (RA) by comparison with (i) (111)In-labelled 1.2B6 F(ab')(2) and (ii) conventional bone scanning. METHODS (99m)Tc-1.2B6-Fab ( approximately 440 MBq) and (111)In-1.2B6-F(ab')(2) ( approximately 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, (99m)Tc-1.2B6-Fab and (99m)Tc-oxidronate ((99m)Tc-HDP) ( approximately 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 (99m)Tc-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 (99m)Tc-Fab was faster than that of (111)In-F(ab')(2) (t(1/2) 142 vs 421 min; P<0.0001). (99m)Tc-Fab appeared somewhat unstable in vivo, as shown by activity in the thyroid gland and bowel. The diagnostic accuracy of (99m)Tc-Fab was 88%, higher than that of (99m)Tc-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 (99m)Tc-Fab discriminates better than (99m)Tc-HDP between actively inflamed and silent joints (Z=4.72; P<0.0001). No uptake of (99m)Tc-Fab was observed by inactive or normal joints, whereas (99m)Tc-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. CONCLUSIONS (99m)Tc-anti-E-selectin-Fab scintigraphy can be used successfully to image synovitis with better specificity than (99m)Tc-HDP bone scanning. The advantages over (111)In-1.2B6-F(ab')(2) are easier availability of the radionuclide, improved physical properties and optimal imaging 4 h after injection.