title: Radiolabeled tirofiban - a potential radiopharmaceutical for detection of deep venous thrombosis.
abstract: OBJECTIVE
  The aim of this study was to investigate the possibility of using99mtechnetium (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 of99mTc-tirofiban to platelets was evaluated. Serum levels of unlabeled (a validated high performance liquid chromatography method) and99mTc-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. When99mTc-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 of99mTc-tirofiban around the place of the induced DVT.
  
  
  CONCLUSIONS
  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 of99mTc-tirofiban may be used to visualize DVT at an early stage.
authors.affiliation: Department of Pharmacy, Faculty of Medical Sciences, Goce Delcev University, Stip; Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Darkovska-Serafimovska
authors.affiliation: Department of Pharmacy, Faculty of Medical Sciences, Goce Delcev University, Stip.
authors.forename: Emilija
authors.initials: E
authors.lastname: Janevik-Ivanovska
authors.affiliation: Department of Physiology, Faculty of Natural Sciences and Mathematics, Ss Cyril and Methodius University in Skopje.
authors.forename: Icko
authors.initials: I
authors.lastname: Djorgoski
authors.affiliation: Department of Pharmacy, Faculty of Medical Sciences, Goce Delcev University, Stip; Department of Quality Control of Medicines, Institute for Public Health of the Republic of Macedonia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Arsova-Sarafinovska
authors.affiliation: Department of Pharmacy, Faculty of Medical Sciences, Goce Delcev University, Stip.
authors.forename: Milka
authors.initials: M
authors.lastname: Zdravkovska
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Ss Cyril and Methodius University in Skopje, Skopje, Republic of Macedonia.
authors.forename: Trajan
authors.initials: T
authors.lastname: Balkanov
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Nenad
authors.initials: N
authors.lastname: Ugresic
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry*; D000818:Animals; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000737:chemistry; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020246:Venous Thrombosis / Q000000981:diagnostic imaging*
chemical_list: D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019275:Radiopharmaceuticals; D014443:Tyrosine; D000244:Adenosine Diphosphate; D000077466:Tirofiban
keywords: 99mtechnetium; deep venous thrombosis; tirofiban; visualization