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Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis
AIM: The aim of this study was to investigate the possibility of using (99m)technetium ((99m)Tc)-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 tirofib...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044985/ https://www.ncbi.nlm.nih.gov/pubmed/27713618 http://dx.doi.org/10.2147/DDDT.S112366 |
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author | Darkovska-Serafimovska, Marija Janevik-Ivanovska, Emilija Djorgoski, Icko Arsova-Sarafinovska, Zorica Zdravkovska, Milka Balkanov, Trajan Ugresic, Nenad |
author_facet | Darkovska-Serafimovska, Marija Janevik-Ivanovska, Emilija Djorgoski, Icko Arsova-Sarafinovska, Zorica Zdravkovska, Milka Balkanov, Trajan Ugresic, Nenad |
author_sort | Darkovska-Serafimovska, Marija |
collection | PubMed |
description | AIM: The aim of this study was to investigate the possibility of using (99m)technetium ((99m)Tc)-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 (99m)Tc-tirofiban to platelets was evaluated. Serum levels of unlabeled (a validated high performance liquid chromatography method) and (99m)Tc-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. (99m)Tc 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 (99m)Tc-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 (99m)Tc-tirofiban around the place of the induced DVT. CONCLUSION: (99m)Tc 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 (99m)Tc-tirofiban may be used to visualize DVT at an early stage. |
format | Online Article Text |
id | pubmed-5044985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50449852016-10-06 Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis Darkovska-Serafimovska, Marija Janevik-Ivanovska, Emilija Djorgoski, Icko Arsova-Sarafinovska, Zorica Zdravkovska, Milka Balkanov, Trajan Ugresic, Nenad Drug Des Devel Ther Original Research AIM: The aim of this study was to investigate the possibility of using (99m)technetium ((99m)Tc)-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 (99m)Tc-tirofiban to platelets was evaluated. Serum levels of unlabeled (a validated high performance liquid chromatography method) and (99m)Tc-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. (99m)Tc 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 (99m)Tc-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 (99m)Tc-tirofiban around the place of the induced DVT. CONCLUSION: (99m)Tc 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 (99m)Tc-tirofiban may be used to visualize DVT at an early stage. Dove Medical Press 2016-09-21 /pmc/articles/PMC5044985/ /pubmed/27713618 http://dx.doi.org/10.2147/DDDT.S112366 Text en © 2016 Darkovska-Serafimovska et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Darkovska-Serafimovska, Marija Janevik-Ivanovska, Emilija Djorgoski, Icko Arsova-Sarafinovska, Zorica Zdravkovska, Milka Balkanov, Trajan Ugresic, Nenad Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis |
title | Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis |
title_full | Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis |
title_fullStr | Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis |
title_full_unstemmed | Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis |
title_short | Radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis |
title_sort | radiolabeled tirofiban – a potential radiopharmaceutical for detection of deep venous thrombosis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044985/ https://www.ncbi.nlm.nih.gov/pubmed/27713618 http://dx.doi.org/10.2147/DDDT.S112366 |
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