Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis

Darkovska-Serafimovska, Marija and Janevik-Ivanovska, Emilija and Djorgoski, Icko and Arsova-Sarafinovska, Zorica and Zdravkovska, Milka and Balkanov, Trajan and Ugresic, Nenad (2016) Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis. Drug Design, Development and Therapy, 2016 (10). pp. 2989-2996. ISSN 1177-8881

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Aim: The 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.
Methods: The 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.
Results: Tirofiban 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.
Conclusion: 99mTc 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.

Keywords: tirofiban, 99mtechnetium, deep venous thrombosis, visualization

Item Type: Article
Subjects: Medical and Health Sciences > Basic medicine
Medical and Health Sciences > Clinical medicine
Medical and Health Sciences > Health biotechnology
Medical and Health Sciences > Health sciences
Divisions: Faculty of Medical Science
Depositing User: Milka Zdravkovska
Date Deposited: 03 Feb 2017 10:12
Last Modified: 03 Feb 2017 10:12

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