Dataset Information

Molecular Detection of Venous Thrombosis in Mouse Models Using SPECT/CT.

ABSTRACT: The efficacy of thrombolysis is inversely correlated with thrombus age. During early thrombogenesis, activated factor XIII (FXIIIa) cross-links α2-AP to fibrin to protect it from early lysis. This was exploited to develop an α2-AP-based imaging agent to detect early clot formation likely susceptible to thrombolysis treatment. In this study, this imaging probe was improved and validated using 111In SPECT/CT in a mouse thrombosis model. In vitro fluorescent- and 111In-labelled imaging probe-to-fibrin cross-linking assays were performed. Thrombus formation was induced in C57Bl/6 mice by endothelial damage (FeCl3) or by ligation (stenosis) of the infrarenal vena cava (IVC). Two or six hours post-surgery, mice were injected with 111In-DTPA-A16 and ExiTron Nano 12000, and binding of the imaging tracer to thrombi was assessed by SPECT/CT. Subsequently, ex vivo IVCs were subjected to autoradiography and histochemical analysis for platelets and fibrin. Efficient in vitro cross-linking of A16 imaging probe to fibrin was obtained. In vivo IVC thrombosis models yielded stable platelet-rich thrombi with FeCl3 and fibrin and red cell-rich thrombi with stenosis. In the stenosis model, clot formation in the vena cava corresponded with a SPECT hotspot using an A16 imaging probe as a molecular tracer. The fibrin-targeting A16 probe showed specific binding to mouse thrombi in in vitro assays and the in vivo DVT model. The use of specific and covalent fibrin-binding probes might enable the clinical non-invasive imaging of early and active thrombosis.

SUBMITTER: Dickhout A

PROVIDER: S-EPMC9221411 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Molecular Detection of Venous Thrombosis in Mouse Models Using SPECT/CT.

Dickhout Annemiek A Van de Vijver Pieter P Bitsch Nicole N van Hoof Stefan J SJ Thomassen Stella L G D SLGD Massberg Steffen S Timmerman Peter P Verhaegen Frank F Koenen Rory R RR Dijkgraaf Ingrid I Hackeng Tilman M TM

Biomolecules 20220613 6

The efficacy of thrombolysis is inversely correlated with thrombus age. During early thrombogenesis, activated factor XIII (FXIIIa) cross-links α2-AP to fibrin to protect it from early lysis. This was exploited to develop an α2-AP-based imaging agent to detect early clot formation likely susceptible to thrombolysis treatment. In this study, this imaging probe was improved and validated using 111In SPECT/CT in a mouse thrombosis model. In vitro fluorescent- and 111In-labelled imaging probe-to-fib ...[more]

PMID: 35740954

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Dataset Information

Molecular Detection of Venous Thrombosis in Mouse Models Using SPECT/CT.

Publications

Molecular Detection of Venous Thrombosis in Mouse Models Using SPECT/CT.

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