Technetium-99m-labeled anti-fibrin DD-3B6/22 Fab' monoclonal antibody fragments, which specifically target human cross-linked fibrin with high affinity, were evaluated in humans for safety and their capacity to detect deep vein thrombi and pulmonary embolism. METHODS: Twenty patients with proven deep-vein thrombosis, documented by contrast venography, or venous duplex scan, were injected with a 600 MBq (0.5 mg) dose of antibody. Planar images of the lower limbs were recorded at 0, 2, 6 and 24 hr and chest scintigrams were recorded at 6 and 24 hr. RESULTS: All venography documented thrombus sites, calves, popliteal and femoral, were detected with the radioimmunoconjugate. For the venous duplex scan-proven thrombus sites, all except two calf thrombi in two patients with bilateral disease and other positive sites were detected. Five patients had bilateral deep-vein thrombosis with multiple sites being visualized with the radioimmunoconjugate in the calf, popliteal and femoral regions. One case of pulmonary embolus was also definitively demonstrated. Documented thrombus sites were detected at 2 and 6 hr postinjection. Nineteen patients were on heparin. No adverse reactions to the injected dose were observed and one low titer human anti-mouse antibody response may have occurred. CONCLUSION: The results indicate that 99mTc-DD-3B6/22 Fab' has potential for noninvasive detection of deep-vein thrombosis and pulmonary embolism.