Currently available ultrasound contrast agents typically comprise microbubble formulations that show great promise for sensitive noninvasive myocardial perfusion imaging. This proposal is focused on the development of a novel targetable particulate ultrasound contrast agent useful for noninvasive delineation of pathological vascular agents. The agent is biotinylated, lipid coated, perfluorocarbon emulsion (250 nm particle) which has low inherent echogenicity unless bound to a surface or itself. A biotinylated monoclonal antibody confers specificity of tissue targeting through an avidin-biotin interaction with the contrast particle in vivo. The agent functions over a wide range of ultrasonic frequencies (5-50 MHz), which extends its utility to transthoracic, transesophageal, and intravascular ultrasonic imaging modalities. The applicants reported recently shown for the first time that sensitive targeting of vascular thrombi is possible in vivo(with as much as 30000 fold contrast enhancement), which provides a paradigm for ultimate extension of this new agent to identification of other tissues such as components of both early and unstable late atherosclerotic lesions. This particulate agent persists for hours in the circulation, which facilitates its binding to targeted tissues, and its safety profile is expected to be suitable for rapid clinical introduction. This proposal aims to: 1) develop enhancements of the formulation to produce a clinically testable product, 2) determine the mechanisms of its effect as a ultrasound contrast agent; and 3) refine and extend its use for imaging pathologic components of atherosclerotic lesions: adhesion molecules, thrombi, and tissue factor. This novel agent should complement the growing number of ultrasound perfusion contrast agents and extend the diagnostic power of ultrasound imaging into the arena of specific and sensitive identification of selected molecular ligands.
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| Winter, Patrick M; Cai, Kejia; Caruthers, Shelton D et al. (2007) Emerging nanomedicine opportunities with perfluorocarbon nanoparticles. Expert Rev Med Devices 4:137-45 |
| Cyrus, Tillmann; Abendschein, Dana R; Caruthers, Shelton D et al. (2006) MR three-dimensional molecular imaging of intramural biomarkers with targeted nanoparticles. J Cardiovasc Magn Reson 8:535-41 |
| Winter, Patrick M; Cai, Kejia; Chen, Junjie et al. (2006) Targeted PARACEST nanoparticle contrast agent for the detection of fibrin. Magn Reson Med 56:1384-8 |
| Hughes, Michael S; Marsh, Jon N; Zhang, Hyuing et al. (2006) Characterization of digital waveforms using thermodynamic analogs: detection of contrast-targeted tissue in vivo. IEEE Trans Ultrason Ferroelectr Freq Control 53:1609-16 |
| Soman, Neelesh R; Marsh, Jon N; Hughes, Michael S et al. (2006) Acoustic activation of targeted liquid perfluorocarbon nanoparticles does not compromise endothelial integrity. IEEE Trans Nanobioscience 5:69-75 |
| Caruthers, Shelton D; Neubauer, Anne M; Hockett, Frank D et al. (2006) In vitro demonstration using 19F magnetic resonance to augment molecular imaging with paramagnetic perfluorocarbon nanoparticles at 1.5 Tesla. Invest Radiol 41:305-12 |
| Lanza, Gregory; Winter, Patrick; Cyrus, Tillmann et al. (2006) Nanomedicine opportunities in cardiology. Ann N Y Acad Sci 1080:451-65 |
| Hughes, Michael S; Marsh, Jon N; Hall, Christopher S et al. (2005) Acoustic characterization in whole blood and plasma of site-targeted nanoparticle ultrasound contrast agent for molecular imaging. J Acoust Soc Am 117:964-72 |
| Morawski, Anne M; Winter, Patrick M; Yu, Xin et al. (2004) Quantitative ""magnetic resonance immunohistochemistry"" with ligand-targeted (19)F nanoparticles. Magn Reson Med 52:1255-62 |
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