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

Timo Heidt, Friederike Braun, Karlheinz Peter, Juergen Goldschmidt, Annette Pethe, Christoph Eugen Hagemeyer, Irene Neudorfer, Andreas Zirlik, Wolfgang A Weber, Christoph Bode, Philipp Tobias Meyer, Martin Behe, Constantin Von Zur Muhlen

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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. Methodology/Principal Findings: LIBS as well as an unspecific control single-chain antibody were labeled with 111Indium (111In) via bifunctional DTPA (= 111In-LIBS/111In-control). Autoradiography after incubation with 111In-LIBS on activated platelets in vitro (mean 3866?28 DLU/mm2, 4010?630 DLU/mm2 and 4520?293 DLU/mm2) produced a significantly higher ligand uptake compared to 111In-control (2101?76 DLU/mm2, 1181?96 DLU/mm2 and 1866?246 DLU/mm2) indicating a specific binding to activated platelets; P
Original languageEnglish
Article numbere18446
Number of pages9
JournalPLoS ONE
Volume6
Issue number3
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Heidt, Timo ; Braun, Friederike ; Peter, Karlheinz ; Goldschmidt, Juergen ; Pethe, Annette ; Hagemeyer, Christoph Eugen ; Neudorfer, Irene ; Zirlik, Andreas ; Weber, Wolfgang A ; Bode, Christoph ; Meyer, Philipp Tobias ; Behe, Martin ; Von Zur Muhlen, Constantin. / Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody. In: PLoS ONE. 2011 ; Vol. 6, No. 3.
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title = "Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody",
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. Methodology/Principal Findings: LIBS as well as an unspecific control single-chain antibody were labeled with 111Indium (111In) via bifunctional DTPA (= 111In-LIBS/111In-control). Autoradiography after incubation with 111In-LIBS on activated platelets in vitro (mean 3866?28 DLU/mm2, 4010?630 DLU/mm2 and 4520?293 DLU/mm2) produced a significantly higher ligand uptake compared to 111In-control (2101?76 DLU/mm2, 1181?96 DLU/mm2 and 1866?246 DLU/mm2) indicating a specific binding to activated platelets; P",
author = "Timo Heidt and Friederike Braun and Karlheinz Peter and Juergen Goldschmidt and Annette Pethe and Hagemeyer, {Christoph Eugen} and Irene Neudorfer and Andreas Zirlik and Weber, {Wolfgang A} and Christoph Bode and Meyer, {Philipp Tobias} and Martin Behe and {Von Zur Muhlen}, Constantin",
year = "2011",
doi = "10.1371/journal.pone.0018446",
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Heidt, T, Braun, F, Peter, K, Goldschmidt, J, Pethe, A, Hagemeyer, CE, Neudorfer, I, Zirlik, A, Weber, WA, Bode, C, Meyer, PT, Behe, M & Von Zur Muhlen, C 2011, 'Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody', PLoS ONE, vol. 6, no. 3, e18446. https://doi.org/10.1371/journal.pone.0018446

Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody. / Heidt, Timo; Braun, Friederike; Peter, Karlheinz; Goldschmidt, Juergen; Pethe, Annette; Hagemeyer, Christoph Eugen; Neudorfer, Irene; Zirlik, Andreas; Weber, Wolfgang A; Bode, Christoph; Meyer, Philipp Tobias; Behe, Martin; Von Zur Muhlen, Constantin.

In: PLoS ONE, Vol. 6, No. 3, e18446, 2011.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody

AU - Heidt, Timo

AU - Braun, Friederike

AU - Peter, Karlheinz

AU - Goldschmidt, Juergen

AU - Pethe, Annette

AU - Hagemeyer, Christoph Eugen

AU - Neudorfer, Irene

AU - Zirlik, Andreas

AU - Weber, Wolfgang A

AU - Bode, Christoph

AU - Meyer, Philipp Tobias

AU - Behe, Martin

AU - Von Zur Muhlen, Constantin

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N2 - 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. Methodology/Principal Findings: LIBS as well as an unspecific control single-chain antibody were labeled with 111Indium (111In) via bifunctional DTPA (= 111In-LIBS/111In-control). Autoradiography after incubation with 111In-LIBS on activated platelets in vitro (mean 3866?28 DLU/mm2, 4010?630 DLU/mm2 and 4520?293 DLU/mm2) produced a significantly higher ligand uptake compared to 111In-control (2101?76 DLU/mm2, 1181?96 DLU/mm2 and 1866?246 DLU/mm2) indicating a specific binding to activated platelets; P

AB - 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. Methodology/Principal Findings: LIBS as well as an unspecific control single-chain antibody were labeled with 111Indium (111In) via bifunctional DTPA (= 111In-LIBS/111In-control). Autoradiography after incubation with 111In-LIBS on activated platelets in vitro (mean 3866?28 DLU/mm2, 4010?630 DLU/mm2 and 4520?293 DLU/mm2) produced a significantly higher ligand uptake compared to 111In-control (2101?76 DLU/mm2, 1181?96 DLU/mm2 and 1866?246 DLU/mm2) indicating a specific binding to activated platelets; P

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