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

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