Imaging of deep venous thrombosis using radioactive-labeled tirofiban

Abstract

The development of radiolabeled small peptide or peptidomimetic ligands can bind platelets and their specifi c expressed receptor have been suggested as a new approach to detect the clot location and, more essentially, to determine the age and morphology of the evolving thrombus. This new approach is focused on the use of a series of radiolabeled platelet GPIIb/IIIa receptor antagonists. Tirofi ban N-(butylsulfonyl)-4-O-(4-(4-piperidyl)-L-tyrosine is a non-peptide tyrosine derivate. The aim of the study was to introduce radioactive-labeled tirofi ban as a specifi c imaging agent for acute DVT. The labeling was performed with technetium-99 in the presence of a stannous reducing agent. The labeled preparation showed fast blood clearance in a normal rat model (without induced thrombosis). More than 80 % of the injected dose was eliminated from the circulation in the fi rst hour after injection. Biodistribution and visualization of the labeled molecule was carried out using an experimental model of thrombosis in a male Wistar rat. Planar images were obtained 30 and 60 min after application of 2 × 10 6 imp/min 99m-technetium-tirofi ban in the rat's tail vein. Sensitivity and specifi city were determined using the ratio of 'left leg positive for DVT' to 'right leg negative for DVT'. The obtained ratio was 1.54 after 30 min and 5.04 after 60 min. These values were considered positive in the detection of acute DVT. The high DVT uptake shows that radiolabeled tirofi ban in the introduced rat model can be a promising agent for imaging the deep venous thrombosis (Fig. 7, Ref. 25).

Development of alternative HPLC method for determination of tirofiban in rat serum

“…Here, 17% of injected doses found 60 minutes after injection in normal rats and the values of 13.27% in rats with DVT confirm the fast clearance of Tirofiban from the blood [14,15]. Our results confirmed the variability between different concentrations of Tirofiban and its metabolite in human samples, especially those obtained from patients with early DVT [23]. In our study, we did not consider determining the serum concentration in humans, so this will be the goal of our next investigation, after receiving the satisfactory result after the first labeling of Tirofiban with radioactive isotopes [23].…”

“…Our results confirmed the variability between different concentrations of Tirofiban and its metabolite in human samples, especially those obtained from patients with early DVT [23]. In our study, we did not consider determining the serum concentration in humans, so this will be the goal of our next investigation, after receiving the satisfactory result after the first labeling of Tirofiban with radioactive isotopes [23]. The good correlation in serum concentrations of different concentrations of Tirofiban obtained from experimental animals and from patients with acute DVT, will contribute to the idea that radiolabeled Tirofiban can be introduce as a potential radiopharmaceutical.…”

“…In our study, besides confirmation of the reciprocity of obtained results from the same injected dose in normal rats and rats with introduced experimental deep venous thrombosis, we attempted to present the impact of different concentration of Tirofiban during the same period. This was important to confirm the biodistribution and fast clearance of Tirofiban in both groups and its potential availability to be used as a radioactive marker for the detection and definition of early deep venous thrombosis [23]. The low concentration of Тirofiban will not affect the fibrinogen binding to the GPIIb/IIIa receptors, but will be enough to visualize the pathological deviations in the circulation [24].…”

Treatment of lower extremity superficial vein thrombosis with low molecular weight heparin

“…Therefore, ultrasound investigation is essential for proper evaluation of the disease. In order to evaluate the deep venous system, other investigation methods, e.g imaging of the deep venous thrombosis using radioactive-labelled tirofi ban, could be used in the future too (6).…”