Ultrasound-based molecular imaging probe for imaging acute myocardial syndromes

描述(由申请人提供)：急性冠脉综合征(ACS)是医疗费用增加的原因，尽管患者的发病率和死亡率仍然相对较高。目前评估急性心肌缺血损伤程度的方法提供了有限的敏感性和特异性，这导致疑似急性冠脉综合征患者的治疗不足和过度治疗。在目前的项目中，我们建议开发一种新的分子成像探针，用于使用超声心动图显示最近的心肌缺血。具体地说，我们的目标是开发一种微泡造影剂，目标是最近缺血的分子标记物。我们已经确定了一种新的靶向配体，并开发了一种生物相容的偶联化学，适合于翻译成人类使用。我们将验证配基结合和微泡稳定性，并在体外和小鼠缺血记忆模型中评估所产生的微泡制剂的靶向效果。这些目标的成功完成将导致一种分子成像探针，可以用来准确和快速地识别最近发生心肌缺血的患者。 公共卫生相关性：近期缺血的成像是心脏护理中一个关键的未得到满足的需求。在目前的项目中，我们的目标是开发一种诊断成像测试，用于使用超声成像检测最近的心肌缺血。该项目的成功将使我们能够快速确定哪些患者将从心肌保留治疗中受益，并为没有经历过缺血事件的患者消除不必要的住院治疗。

DESCRIPTION (provided by applicant): Acute coronary syndromes (ACS) account 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 probe for visualization of recent myocardial ischemia using echocardiography. Specifically, we aim to develop a microbubble contrast agent targeted to a molecular marker of recent ischemia. We have identified a novel targeting ligand, and developed a biocompatible coupling chemistry suitable for translation to human use. We will validate ligand conjugation and microbubble stability, and assess the targeting efficacy of the resultant microbubble formulations in vitro and in a mouse model of ischemic memory. Successful completion of these aims will result in a molecular imaging probe that may be used to accurately and rapidly identify patients with recent myocardial ischemia. PUBLIC HEALTH RELEVANCE: 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 an ischemic event.