Imaging of deep venous thrombosisusingradioactive labeled Tirofiban: animal model evaluation

Imaging of acute thrombus, especially the very prevalent condition of acute deep vein thrombosis is usually relied on conventional imaging techniques utilizing either ultrasonography or contrast venography. The former procedure is limited by accuracy and the latter by technical considerations. Recent advances in the understanding of the pathogenesis of acute clot at the molecular level have suggested new opportunities for detection of the acute thrombotic process based on the biomolecular behavior of components of the clotting process including the formed element of the blood, the platelet. Thus, development of radiolabelled small peptide or peptidomimetic ligandsthat can bind platelets and their specific expressed receptor have been suggested as a new approach to detect clot location and, more essentially, determine the age andmorphology of the evolving thrombus. This new approach has focused on the use of aseries of radiolabelled platelet GPIIb/IIIa receptor antagonists. Tirofiban N-(butylsulfonyl)-4-O-(4-(4-piperidyl)-L-tyrosine is a non-peptide tyrosine derivate. The aim of thestudy was to introduce radioactive labelled tirofiban as a specific imaging agent foracute DVT. The labeling was performed with Technetium-99 in the presence of a stannousreducing agent. The labelled preparation showed a fast blood clearance in the normal rat model (without induced thrombosis). More than 80%of the injected dose was eliminated from the circulation in the first hour after injection.Biodistribution and visualization of the labelled molecule was carried out using anexperimental model of thrombosis in the male Wistar rat. Planar images were obtained30 min and 60 min after application of 2 × 106 imp/min 99mTechnetium-tirofiban, in the rat’s tail vein. Sensitivityand specificity were determined using the ratio ‘left leg positive for DVT’ and ‘right legnegative for DVT’. The obtained ratio was 1.54 after 30 min and 5.04 after 60 min. These values were considered as positive in the detection of acuteDVT. The highDVT uptake show that radiolabelled tirofiban in the introduced rat model can be the promising agent for imaging of deep venous thrombosis