Ultrasound-based molecular imaging probe for imaging acute myocardial syndromes

用于急性心肌综合征成像的超声分子成像探针

• 批准号: 8200924
• 负责人: Joshua J. Rychak
• 金额: $ 25.97万
• 依托单位: TARGESON, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8200924
• 关键词: Accounting; Acute; Adhesions; Affinity; Amides; Animal Model; Antibodies; Area; Binding; Biocompatible; Biological Assay; Blocking Antibodies; Blood flow; C57BL/6 Mouse; Cardiac; Caring; Characteristics; Charge; Chemistry; Chimeric Proteins; Contrast Media; Coupling; Detection; Diagnostic Imaging; Drug Formulations; Echocardiography; Enzyme-Linked Immunosorbent Assay; Evaluation; Event; Exhibits; Flow Cytometry; Healthcare; Hospitalization; Human; Image; Imagery; Imaging Techniques; Immunoglobulin G; Immunohistochemistry; In Vitro; Incubated; Inflammation; Injury; Ischemia; Kinetics; Knockout Mice; Ligands; Ligation; Liquid substance; Mediating; Memory; Methods; Microbubbles; Molecular Weight; Morbidity - disease rate; Mus; Myocardial; Myocardial Ischemia; Myocardial perfusion; Myocardium; P-Selectin; P-selectin ligand protein; Patients; Perfusion; Physiologic pulse; Physiological; Recombinants; Relative (related person); Selectins; Sensitivity and Specificity; Site; Specificity; Surface; Syndrome; Testing; Translations; Ultrasonography; Work; acute coronary syndrome; base; cohort; density; experience; imaging probe; man; molecular imaging; molecular marker; mortality; mouse model; novel; pre-clinical; research study; shear stress; success; thioether

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.

描述（由申请人提供）：尽管患者发病率和死亡率仍然相对较高，但急性冠状动脉综合征（ACS）导致医疗费用水平不断上升。目前评估急性情况下心脏缺血性损伤程度的方法的敏感性和特异性有限，这导致对疑似 ACS 患者的治疗不足和过度。在当前的项目中，我们建议开发一种新型分子成像探针，用于使用超声心动图可视化近期心肌缺血。具体来说，我们的目标是开发一种针对近期缺血分子标记物的微泡造影剂。我们已经确定了一种新型靶向配体，并开发了一种适合转化为人类使用的生物相容性偶联化学物质。我们将验证配体缀合和微泡稳定性，并评估所得微泡制剂在体外和缺血记忆小鼠模型中的靶向功效。成功完成这些目标将产生一种分子成像探针，可用于准确、快速地识别近期心肌缺血的患者。 PUBLIC HEALTH RELEVANCE: Imaging of recent ischemia is a critical unmet need in cardiac care.在当前的项目中，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近期心肌缺血。该项目的成功将能够快速识别可从心肌保留治疗中受益的患者，并消除未经历缺血事件的患者不必要的住院治疗。