Combined Therapeutic-Imaging Agent for Atherosclerosis

动脉粥样硬化联合治疗显像剂

• 批准号: 6950739
• 负责人: Gregory M Lanza
• 金额: $ 37.99万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-22 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6950739
• 关键词: angiogenesis inhibitors; antiatherogenic agent; atherosclerosis; atherosclerotic plaque; bioimaging /biomedical imaging; cardiovascular disorder chemotherapy; cardiovascular imaging /visualization; dosage; drug delivery systems; drug screening /evaluation; integrins; laboratory rabbit; magnetic resonance imaging; molecular /cellular imaging; molecular probes; nanotechnology; nonhuman therapy evaluation; pharmacokinetics; technology /technique development

DESCRIPTION (provided by applicant): For decades, the association of angiogenesis and atherosclerosis has been well known. Expansion of the network of small capillaries that perfuse the wall of larger blood vessels, the vasa vasorum, is recognized in diseases of chronic inflammation (e.g., atherosclerosis) and injury (e.g., angioplasty). Many hypothesize that the inward penetration of neo-vasculature within the arterial wall promotes plaque growth, intra-plaque hemorrhage, and lesion instability. This cascade of events precipitates intra-luminal thrombosis and thromboembolism, which are the proximate causes of myocardial infarction and stroke. Thus, plaque angiogenesis may be the linchpin pathology for the acute complications of atherosclerosis. The ultimate aims of this proposal involve magnetic resonance molecular imaging of plaque neo-vasculature in conjunction with local anti-angiogenesis therapy. Specifically, alpha v beta 3 -targeted paramagnetic nanoparticles will be used to spatially localize and quantify early atherosclerotic burdens in hyperlipidemic New Zealand White rabbits and to deliver fumagillin to elicit a marked antiangiogenic effect. The project will explore the potential of HMG-Coa reductase inhibitors to sustain the acute "atherolytic" response of targeted fumagillin therapy and will evaluate the safety, pharmacokinetics and pharmacodynamics of this technology. This novel application of molecular imaging and targeted drug delivery could serve as part of a primary prevention strategy to diagnose, treat, and monitor early atherosclerosis.

描述（由申请人提供）： 几十年来，血管生成和动脉粥样硬化的关联已众所周知。在慢性炎症（例如动脉粥样硬化）和损伤（例如血管成形术）疾病中发现了灌注较大血管壁（血管滋养管）的小毛细血管网络的扩张。许多假设认为，动脉壁内新血管系统的向内渗透促进了斑块生长、斑块内出血和病变不稳定。这一级联事件促使管腔内血栓形成和血栓栓塞，这是心肌梗塞和中风的直接原因。因此，斑块血管生成可能是动脉粥样硬化急性并发症的关键病理学。 该提案的最终目标涉及斑块新血管系统的磁共振分子成像与局部抗血管生成治疗相结合。具体而言，α v beta 3 靶向顺磁纳米颗粒将用于空间定位和量化高脂血症新西兰白兔的早期动脉粥样硬化负担，并递送夫马洁林以引发显着的抗血管生成作用。该项目将探索 HMG-Coa 还原酶抑制剂维持靶向夫马洁林治疗的急性“动脉粥样硬化”反应的潜力，并将评估该技术的安全性、药代动力学和药效学。分子成像和靶向药物输送的这种新应用可以作为诊断、治疗和监测早期动脉粥样硬化的一级预防策略的一部分。