Targeted microbubbles: Ultrasound contrast agents for molecular imaging and drug delivery

NUCL 98

Alexander L. Klibanov, alk6n@virginia.edu1, JJ. Rychak2, YK. Cho3, S Alikhani2, WC. Yang2, JR. Lindner4, J. Hossack2, and K. Ley3. (1) Deptartment of Internal Medicine (Cardiovascular Division), University of Virginia, Hospital Drive, Cobb Hall, RM 1026, Charlottesville, VA 22908, (2) Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, (3) Cardiovascular Research Center, University of Virginia, (4) Cardiovascular Division, Oregon Health and Sciences University, Portland, OR
Ultrasound imaging offers inexpensive portable technology to detect gas-filled microbubbles within the vasculature. Detection of single micron-sized particles (picogram mass) is achieved with existing clinical scanners. Therefore, imaging of targeted ligand-carrying bubbles selectively attached to the regions of upregulation of specific receptors becomes feasible. We prepare stable gas-filled microbubbles stabilized with a lipid monolayer and PEG brush. Particles are outfitted with targeting ligands: antibodies, peptides, carbohydrate derivatives via avidin-biotin link or covalently. Ligand-microbubbles selectively attach to surfaces that present P- or E-selectins, ICAM-1, VCAM-1 or MAdCAM-1. Antibodies allow firm attachment of targeted microbubbles. Rapid binding is necessary to achieve microbubble targeting under flow and can be achieved via PSGL-1 fragments or via polymerized Sialyl Lewis X. In vivo targeting of microbubbles enables delineation and imaging of areas of inflammation. Ultrasound-assisted drug release from microbubble particles allows externally-triggered tissue deposition of pharmaceuticals, which may improve efficacy and specificity of therapeutic interventions.
 

Recent Advances in Molecular Imaging
1:25 PM-5:00 PM, Wednesday, 13 September 2006 Moscone Center -- Room 272, Oral

Division of Nuclear Chemistry & Technology

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006