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Proceedings Paper

Site-targeted acoustic contrast agent detects molecular expression of tissue factor after balloon angioplasty
Author(s): Christopher S. Hall; Dana R. Abendschein; David E. Scherrer; Michael J. Scott; Jon N. Marsh; Samuel A. Wickline; Gregory M. Lanza
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Paper Abstract

Complex molecular signaling heralds the early stages of pathologies such as angiogenesis, inflammation, and cellular responses to mechanically damaged coronary arteries after balloon angioplasty. In previous studies, we have demonstrated acoustic enhancement of blood clot morphology with the use of a nongaseous, ligand-targeted acoustic nanoparticle emulsion delivered to areas of thrombosis both in vitro and in vivo. In this paper, we characterize the early expression of tissue factor which contributes to subsequent arterial restenosis. Tissue factor is a 42kd glycoprotein responsible for blood coagulation but also plays a well-described role in cancer metastasis, angiogenesis, and vascular restenosis. This study was designed to determine whether the targeted contrast agent could localize tissue factor expressed within the wall of balloon-injured arteries. Both carotid arteries of five pigs (20 kg) were injured using an 8 X 20 mm angioplasty balloon. The carotids were treated in situ with a perfluorocarbon nanoparticle emulsion covalently complexed to either specific anti-tissue factor polyclonal F(ab) fragments (treatment) or non-specific IgG F(ab) fragments (control). Intravascular ultrasound (30 MHz) images of the arteries were obtained before and after exposure to the emulsions. Tissue- factor targeted ultrasonic contrast agent acoustically enhanced the subintima and media at the site of balloon- induced injury compared with control contrast arteries (p less than 0.05). Immunohistochemical staining confirmed the presence of increased tissue factor at the sites of acoustic enhancement. Binding of the targeted agents was demonstrated in vitro by scanning electron microscope images of cultured smooth muscle cells that constitutively express tissue factor. This study demonstrates the concept of molecular imaging and localization of carotid arteries' tissue factor in vivo using a new, nanoparticulate emulsion. Enhancement of the visualization of the molecular expression of tissue factor could prove to be a prognostically important predictor of subsequent restenosis. Moreover, with the incorporation of specific drug treatments into the nanoparticulate contrast agent, ultrasonic molecular imaging may yield reliable detection and quantification of nascent pathologies and facilitate targeted drug therapy.

Paper Details

Date Published: 12 April 2000
PDF: 8 pages
Proc. SPIE 3982, Medical Imaging 2000: Ultrasonic Imaging and Signal Processing, (12 April 2000); doi: 10.1117/12.382241
Show Author Affiliations
Christopher S. Hall, Washington Univ. School of Medicine (United States)
Dana R. Abendschein, Washington Univ. School of Medicine (United States)
David E. Scherrer, Washington Univ. School of Medicine (United States)
Michael J. Scott, Washington Univ. School of Medicine (United States)
Jon N. Marsh, Washington Univ. School of Medicine (United States)
Samuel A. Wickline, Washington Univ. School of Medicine (United States)
Gregory M. Lanza, Washington Univ. School of Medicine (United States)


Published in SPIE Proceedings Vol. 3982:
Medical Imaging 2000: Ultrasonic Imaging and Signal Processing
K. Kirk Shung; Michael F. Insana, Editor(s)

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