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Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody.

Identifieur interne : 001608 ( Main/Exploration ); précédent : 001607; suivant : 001609

Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody.

Auteurs : RBID : pubmed:21479193

English descriptors

Abstract

Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis.

DOI: 10.1371/journal.pone.0018446
PubMed: 21479193

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Le document en format XML

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<title xml:lang="en">Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody.</title>
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<name sortKey="Heidt, Timo" uniqKey="Heidt T">Timo Heidt</name>
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<nlm:affiliation>Department of Cardiology and Angiology, University of Freiburg, Freiburg, Germany. timo.heidt@uniklinik-freiburg.de</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Cardiology and Angiology, University of Freiburg, Freiburg</wicri:regionArea>
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<name sortKey="Deininger, Friederike" uniqKey="Deininger F">Friederike Deininger</name>
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<name sortKey="Peter, Karlheinz" uniqKey="Peter K">Karlheinz Peter</name>
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<name sortKey="Goldschmidt, J Rgen" uniqKey="Goldschmidt J">Jürgen Goldschmidt</name>
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<name sortKey="Pethe, Annette" uniqKey="Pethe A">Annette Pethe</name>
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<name sortKey="Hagemeyer, Christoph E" uniqKey="Hagemeyer C">Christoph E Hagemeyer</name>
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<name sortKey="Neudorfer, Irene" uniqKey="Neudorfer I">Irene Neudorfer</name>
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<name sortKey="Zirlik, Andreas" uniqKey="Zirlik A">Andreas Zirlik</name>
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<name sortKey="Weber, Wolfgang A" uniqKey="Weber W">Wolfgang A Weber</name>
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<name sortKey="Bode, Christoph" uniqKey="Bode C">Christoph Bode</name>
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<name sortKey="Meyer, Philipp T" uniqKey="Meyer P">Philipp T Meyer</name>
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<name sortKey="Behe, Martin" uniqKey="Behe M">Martin Behe</name>
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<term>Carotid Artery Thrombosis (physiopathology)</term>
<term>Carotid Artery Thrombosis (radiography)</term>
<term>Carotid Artery Thrombosis (radionuclide imaging)</term>
<term>Epitopes (immunology)</term>
<term>Indium Radioisotopes</term>
<term>Isotope Labeling (methods)</term>
<term>Mice</term>
<term>Platelet Activation (physiology)</term>
<term>Protein Binding</term>
<term>Single-Chain Antibodies (diagnostic use)</term>
<term>Tomography, Emission-Computed, Single-Photon</term>
<term>Tomography, X-Ray Computed</term>
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<term>Single-Chain Antibodies</term>
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<term>Epitopes</term>
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<term>Platelet Activation</term>
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<term>Carotid Artery Thrombosis</term>
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<term>Carotid Artery Thrombosis</term>
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<term>Carotid Artery Thrombosis</term>
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<term>Animals</term>
<term>Autoradiography</term>
<term>Indium Radioisotopes</term>
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<front>
<div type="abstract" xml:lang="en">Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis.</div>
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<Title>PloS one</Title>
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<ArticleTitle>Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody.</ArticleTitle>
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<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis.</AbstractText>
<AbstractText Label="METHODOLOGY/PRINCIPAL FINDINGS" NlmCategory="RESULTS">LIBS as well as an unspecific control single-chain antibody were labeled with (111)Indium ((111)In) via bifunctional DTPA ( = (111)In-LIBS/(111)In-control). Autoradiography after incubation with (111)In-LIBS on activated platelets in vitro (mean 3866 ± 28 DLU/mm(2), 4010 ± 630 DLU/mm(2) and 4520 ± 293 DLU/mm(2)) produced a significantly higher ligand uptake compared to (111)In-control (2101 ± 76 DLU/mm(2), 1181 ± 96 DLU/mm(2) and 1866 ± 246 DLU/mm(2)) indicating a specific binding to activated platelets; P<0.05. Applying these findings to an ex vivo mouse model of carotid artery thrombosis revealed a significant increase in ligand uptake after injection of (111)In-LIBS in the presence of small thrombi compared to the non-injured side, as confirmed by histology (49630 ± 10650 DLU/mm(2) vs. 17390 ± 7470 DLU/mm(2); P<0.05). These findings could also be reproduced in vivo. SPECT-CT analysis of the injured carotid artery with (111)In-LIBS resulted in a significant increase of the target-to-background ratio compared to (111)In-control (1.99 ± 0.36 vs. 1.1 ± 0.24; P < 0.01).</AbstractText>
<AbstractText Label="CONCLUSIONS/SIGNIFICANCE" NlmCategory="CONCLUSIONS">Nuclear imaging with (111)In-LIBS allows the detection of platelet activation in vitro and ex vivo with high sensitivity. Using SPECT-CT, wall-adherent activated platelets in carotid arteries could be depicted in vivo. These results encourage further studies elucidating the role of activated platelets in plaque pathology and atherosclerosis and might be of interest for further developments towards clinical application.</AbstractText>
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