In vivo molecular imaging of stretch-induced tissue factor in carotid arteries with ligand-targeted nanoparticles

Molecular imaging permits tissues to be functionally characterized by ident ification of specific cell-surface receptors with targeted contrast agents. In our study, a ligand-targeted acoustic nanoparticle system was used to i dentify the angioplasty-induced expression of tissue factor by smooth muscl e cells within the tunica media. Pig carotid arteries were overstretched bi laterally with balloon catheters, treated with a tissue factor-targeted, or a control nanoparticle system, and imaged with intravascular ultrasound (2 0 MHz) before and after treatment. Carotid wall acoustic reflectivities wer e unaffected by overstretch injury. Tissue factor-targeted nano-emulsion bo und and increased the echogenicity of smooth muscle cells expressing tissue factor within the tunica media. The targeted emulsion increased the arteri al wall. gray scale (99.4 +/- 14.5; P < .05) relative to pretreatment (41.8 +/- 11.1, P < 0.05) and the control gray scale (pre-emulsion: 49.3 +/- 9.5 ; post-emulsion: 43.7 +/- 6.4; P < .05). The area of acoustic enhancement a ppeared to coincide with expression of induced tissue factor in the tunica media confirmed by Immunohistochemistry. We have demonstrated that this nov el nanoemulsion can infiltrate into arterial walls after balloon injury and localize the expression of overstretch-induced tissue factor within pig ca rotid arteries. Molecular imaging and quantification of complex, biochemica l change, such as tissue factor expression after angioplasty, may prove to be a prognostically important predictor of subsequent restenosis.