Acute coronary syndrome (ACS) accounts for an increasing level of healthcare expense, although patient morbidity and mortality remain relatively high. Current methods for assessing the extent of cardiac ischemic injury in an acute setting offer limited sensitivity and specificity, which leads to both under- and over-treatment of patients with suspected ACS. In the current project, we propose to develop a novel molecular imaging agent for visualization of recent myocardial ischemia using echocardiography. Specifically, we aim to develop an ultrasound contrast agent targeted to a molecular marker of recent ischemia. In Phase I of this project, we synthesized a contrast agent bearing a selectin-binding ligand, confirmed its target-binding activity in vitro, and demonstrated specific uptake in a mouse model of myocardial ischemic injury. In Phase II, we propose to develop the synthetic and analytical methodology to allow for clinical-scale manufacture of this agent, perform single-dose toxicology studies in two species, characterize the behavior of our imaging agent in mouse models of complex coronary disease, and validate imaging efficacy using clinical-scale imaging equipment in a closed- chest canine model. Successful completion of these aims will result in a molecular imaging agent that may be used to accurately and rapidly identify patients with recent myocardial ischemia.
Imaging of recent ischemia is a critical unmet need in cardiac care. In the current project, we aim to develop a diagnostic imaging test for detecting recent myocardial ischemia using ultrasound imaging. Success in this project will enable rapid identification of patients who would benefit from myocardium-sparing treatments, and eliminate unnecessary hospitalizations for patients who have not experienced a true ischemic event.
| Rychak, Joshua J; Klibanov, Alexander L (2014) Nucleic acid delivery with microbubbles and ultrasound. Adv Drug Deliv Rev 72:82-93 |
