TARGETED MICROBUBBLES FOR DIAGNOSIS OF VASCULAR CLOTS

用于诊断血管凝块的靶向微泡

• 批准号: 6184173
• 负责人: Terry Onichi Matsunaga
• 金额: $ 29.03万
• 依托单位: IMARX THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6184173
• 关键词: baboons; cardiovascular disorder chemotherapy; cardiovascular disorder diagnosis; chemical synthesis; contrast media; diagnosis design /evaluation; dogs; drug delivery systems; drug design /synthesis /production; high performance liquid chromatography; laboratory rat; mass spectrometry; microcapsule; nuclear magnetic resonance spectroscopy; thrombosis; ultrasound therapy

Vascular occlusions secondary to thrombi (blood clots) are predisposing factors to strokes, myocardial infarctions, and vascular thrombosis. Mortality for strokes and heart attacks in the United States number 3.4 million annually while morbidity associated with these diseases results in paralysis and loss of motor and cognitive functions. Clearly, more reliable diagnosis and treatment are needed. Recently, we have developed targeted microbubbles for diagnostic ultrasound to detect vascular clots. The targeting ligand on the microbubbles for the IIIa subcomponent of the GPIIbIIIa receptor on thrombi. Phase I efforts have demonstrated feasibility for these targeted microbubbles to bind selectively to thrombi both in vitro and in vivo for ultrasound detection. Experiments have also indicated that these microbubbles may also be useful for therapeutic applications such as sonothrombolysis and drug delivery. The objectives of this Phase II application are: 1) Synthesize a series of targeting ligand analogs with improved binding and stability properties; 2) Characterize these analogs by a variety of physical techniques; 3) Perform detailed acoustic studies; 4) Develop an vitro binding assay to determine microbubble binding efficiency; 5) Perform in vivo experiments in rodent, primate and canine models; and 6) perform acute and chronic toxicity studies in the rodent model. PROPOSED COMMERCIAL APPLICATIONS: Products and techniques with commercial applicability from these thrombus targeting studies will directly lead to the development of one or more thrombus-specific intravascular contrast agents. In addition, it is envisioned that new catheters, stents, peripheral vascular devices and thrombolytic agents will be developed to complement the introduction of new contrast agents.

继发于血栓（血凝块）的血管闭塞是中风、心肌梗塞和血管血栓形成的诱发因素。在美国，每年有 340 万人死于中风和心脏病，而与这些疾病相关的发病率会导致瘫痪以及运动和认知功能丧失。显然，需要更可靠的诊断和治疗。最近，我们开发了用于诊断超声的靶向微泡，以检测血管凝块。微泡上针对血栓上 GPIIbIIIa 受体 IIIa 亚组分的靶向配体。第一阶段的工作已经证明了这些靶向微泡在体外和体内选择性地与血栓结合以进行超声检测的可行性。实验还表明，这些微泡也可用于治疗应用，例如超声溶栓和药物输送。本次二期申请的目标是： 1) 合成一系列具有改进的结合和稳定性特性的靶向配体类似物； 2) 通过各种物理技术表征这些类似物； 3) 进行详细的声学研究； 4) 开发体外结合测定法以确定微泡结合效率； 5) 进行啮齿动物、灵长类动物和犬类模型的体内实验； 6) 在啮齿动物模型中进行急性和慢性毒性研究。拟议的商业应用：这些血栓靶向研究具有商业适用性的产品和技术将直接导致一种或多种血栓特异性血管内造影剂的开发。此外，预计将开发新的导管、支架、外周血管装置和溶栓剂，以补充新造影剂的引入。