Accuracy and safety of ^99mTc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis: A phase II study

Background: The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. ^99mTc-labelled DI-DD3B6/22-80B3 Fab́ fragments ( ^99mTc-DI-80B3, ThromboView®) is a novel diagnostic test that uses a radiolabelled humanized monoclonal antibody fragment specific for the D-dimer region of cross-linked fibrin to detect DVT. This test has an anatomic component to locate DVT and a functional component to differentiate acute (newly formed) thrombus from inactive (old) thrombus. Methods: In a multi-centre prospective cohort trial we investigated the diagnostic accuracy and safety of ^99mTc-DI-80B3 in consecutive patients with suspected DVT who had the diagnosis confirmed or excluded by venography. Results: We enrolled 94 patients with suspected DVT of whom 12 did not have ^99mTc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 ^99mTc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. ^99mTc-DI-80B3 imaging was well-tolerated: 2 patients developed urticaria; none developed serious adverse events. For proximal DVT, the sensitivity (84.2%; 95% confidence interval [CI]: 62.4-94.5) and specificity (97.6%; CI: 83.3-99.4) were highest when the combined 0.25-hour and 3-hour ^99mTc-DI-80B3 images were used. The accuracy was lower for distal DVT, irrespective of the images used. There were insufficient patients to comment on the accuracy of ^99mTc-DI-80B3 imaging for suspected recurrent DVT. Conclusions: ^99mTc-DI-80B3 (ThromboView®) is a novel diagnostic modality for patients with suspected DVT with a promising accuracy and safety profile that justifies additional clinical development in diagnostic accuracy and clinical management studies.