Methods in Molecular Imaging and Targeted Therapeutics

分子成像和靶向治疗方法

• 批准号: 7459564
• 负责人: SAMUEL A WICKLINE
• 金额: $ 153.36万
• 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: 2004-07-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7459564
• 关键词: Acute; Apolipoprotein E; Arterial Fatty Streak; Atherosclerosis; Avidity; Benchmarking; Binding; Biodistribution; Biomedical Research; Blood Platelets; Chemicals; Cholesterol; Clinical; Clinical Trials; Contrast Media; Coupled; Data; Deposition; Detection; Development; Diet; Disease regression; Dose; Drug Formulations; Drug Kinetics; Early Diagnosis; Emulsions; Epitopes; Evaluation; Fluorine; Fluorocarbons; Genetic; Goals; Growth; Image; Imagery; Incidence; Integrins; Kinetics; Lead; Lesion; Ligand Binding; Ligands; Lipids; Localized; Magnetic Resonance Imaging; Medical; Medical Imaging; Methods; Modeling; Molecular; Molecular Target; Mus; Myocardial Infarction; NIH Program Announcements; Nanotechnology; Oryctolagus cuniculus; Outpatients; P-Selectin; Pathology; Patients; Protons; Range; Recombinants; Request for Proposals; Research; Safety; Schedule; Signal Transduction; Site; Spectrum Analysis; Sterility; Stroke; System; Technology; Testing; Therapeutic; Therapeutic Agents; Thrombosis; Time; Toxic effect; Vascular Cell Adhesion Molecule-1; angiogenesis; base; commercialization; feeding; glycyl-glycyl-glycine; intravital fluorescence microscopy; molecular imaging; nanoparticle; novel; pre-clinical; targeted delivery; therapeutic target

DESCRIPTION (provided by applicant): The broad subject of this Biomedical Research Partnership (BRP) application is the development of novel multidimensional nanotechnologies for sensitive and specific imaging of molecular epitopes that are etiologic for atherosclerosis. The unifying hypothesis is that targeted molecular imaging with novel paramagnetic perfluorocarbon emulsion nanoparticle contrast agents can delineate selected molecular features of atherosclerotic lesions that are critical determinants of early lesion growth and later lesion instability. Noninvasive and early detection of these situations could enhance patient management and potentially reduce the incidence of myocardial infarction and stroke. The long-range goal is to produce a targeted nanoparticle contrast agent characterized by: 1) flexible targeting options depending on the binding ligand selected, 2) flexible imaging choices based on contrast mechanism best suited to the pathology in question, and 3) flexible opportunities for local delivery of therapeutic agents coupled directly with image-based quantification of local nanoparticle deposition. The technology is expected to enable early noninvasive detection of a variety of pathologies, convenient serial outpatient evaluation, and site-targeted delivery of therapeutics as clinically indicated. Stable and safe self-assembling nanoparticles will be developed, refined, and tested for visualization of pathological epitopes with the use of magnetic resonance imaging (MRI). Corporate partners who are involved in the research and intended commercialization are Kereos, Inc., Philips Medical Systems, Bristol-Myers Squibb Medical Imaging, and Dow Chemical.

描述（由申请人提供）： 这种生物医学研究伙伴关系（BRP）应用的广泛主题是开发新型的多维纳米技术，用于对动脉粥样硬化的病因学分子表位的敏感和特定成像。统一的假设是，具有新型顺磁性全氟化合物乳液纳米粒子对比剂的靶向分子成像可以描绘动脉粥样硬化病变的选定分子特征，这些分子特征是早期病变生长和后来病变不稳定的关键决定性。对这些情况的无创和早期发现可以增强患者的管理，并有可能降低心肌梗塞和中风的发生率。远程目标是产生一个有针对性的纳米颗粒对比剂，其特征是：1）根据所选的绑定配体的灵活靶向选项，2）基于最适合所讨论病理的对比机制的灵活成像选择，而3）3）柔性机会，可灵活地与局部与基于图像基于图像的量定量化的局部治疗剂交付局部量化局部NanAnanoportions的局部治疗剂。预计该技术将在临床上指出的各种病理，方便的串行门诊评估以及针对现场的治疗剂的递送，使其早期非侵入性检测。通过使用磁共振成像（MRI），将开发，完善和测试稳定且安全的自组装纳米颗粒。参与研究和预期商业化的公司合作伙伴是Kereos，Inc。，Philips Medical Systems，Bristol-Myers Squibb Medical Imageing和Dow Chemical。