Restricted Access
Reason: Access restricted by the author. A copy can be requested for private research and study by contacting your institution's library service. This copy cannot be republished
Novel single-chain antibody-targeted microbubbles for molecular ultrasound imaging of thrombosis and thrombolysis.
thesis
posted on 2017-02-06, 02:55 authored by Wang, XiaoweiMolecular imaging is a fast emerging technology allowing non-invasive detection of vascular pathologies. However, imaging modalities offering high resolution currently do not allow real-time imaging. We hypothesized that contrast enhanced ultrasound with microbubbles selectively targeted to activated platelets would offer high-resolution, real-time molecular imaging of evolving and dissolving arterial thrombi.
Lipid-shell based gas-filled microbubbles (MB) were conjugated to either a single-chain antibody (scFv) specific for activated GPIIb/IIIa via binding to a Ligand-Induced Binding Site (LIBS-MB), or a non-specific scFv (control-MB). LIBS-MB, but not control-MB, strongly adhered to both immobilized activated platelets and micro-thrombi under flow. Thrombi, induced in carotid arteries of C57Bl6-mice in vivo by ferric chloride injury, were then assessed with ultrasound before and 20 minutes after MB injection, using grayscale area intensity measurement. Grayscale units converted to decibels demonstrated a significant increase after LIBS-MB but not after control-MB injection (p<0.001). Furthermore after thrombolysis with urokinase, LIBS-MB ultrasound-imaging allows monitoring of the reduction of thrombus size (p<0.001). A lower systematic dose of targeted fibrinolytic agent is required to achieve the same fibrinolytic potency.
We demonstrate that GPIIb/IIIa-targeted microbubbles specifically bind to activated platelets in vitro and allow real-time molecular imaging of acute arterial thrombosis as well as monitoring of pharmacological thrombolysis in vivo. This non-invasive and cost effective imaging modality provides a unique approach to rapidly detect (micro)thrombi with high resolution, allowing for early diagnosis and therapy, as well as enabling the fast identification of success or failure of thrombolytic therapy.
History
Principal supervisor
Karlheinz PeterAdditional supervisor 1
Vhristoph Hagemeyer, Ingo AhnensYear of Award
2012Department, School or Centre
Baker IDI Heart and Diabetes InstituteCampus location
AustraliaCourse
Doctor of PhilosophyDegree Type
DOCTORATEFaculty
Faculty of Medicine Nursing and Health SciencesUsage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC