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).

AimThe aim of this study was to investigate the possibility of using 99mtechnetium (99mTc)-labeled tirofiban (a reversible antagonist of glycoprotein IIb/IIIa) for detection of deep venous thrombosis (DVT) in rats without causing an antiplatelet effect.MethodsThe ability of in vitro tirofiban to inhibit adenosine 5′-diphosphate (ADP)-induced platelet aggregation was evaluated using optical aggregometer. Binding of 99mTc-tirofiban to platelets was evaluated. Serum levels of unlabeled (a validated high performance liquid chromatography method) and 99mTc-tirofiban after single intravenous injection were evaluated in male Wistar rats with or without induced DVT (femoral vein ligation model), and the rats were also subjected to whole body scintigraphy.ResultsTirofiban in vitro inhibits ADP-induced aggregation of human platelets in a dose- and concentration-dependent manner (10 nM to 2 μM), but only if it is added before ADP and not after ADP. 99mTc labeling did not affect the ability of tirofiban to bind to either human or rat platelets, nor did it affect tirofiban pharmacokinetics in intact rats or in animals with induced DVT. When 99mTc-tirofiban was injected to rats after induction of DVT, at a molar dose lower than the one showing only a weak antiaggregatory effect in vitro, whole body scintigraphy indicated localization of 99mTc-tirofiban around the place of the induced DVT.Conclusion99mTc labeling of tirofiban does not affect its ability to bind to glycoprotein IIb/IIIa or its in vivo pharmacokinetics in rats, either intact or with DVT. A low, nonantiaggregatory dose of 99mTc-tirofiban may be used to visualize DVT at an early stage.