Ultrasound Imaging and Local Drug Delivery in Tumors

肿瘤的超声成像和局部药物输送

• 批准号: 7237894
• 负责人: Katherine W Ferrara
• 金额: $ 136.43万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-25 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7237894
• 关键词: Acoustics; Adhesions; Advanced Development; Antibodies; Area; Biodistribution; Biological Assay; Blood Vessels; Caliber; California; Capillary Permeability; Cellular biology; Chemistry; Cherry - dietary; Clinical; Communities; Contrast Media; Development; Dimensions; Doctor of Pharmacy; Doctor of Philosophy; Drug Carriers; Drug Delivery Systems; Drug Labeling; Drug vehicle; Endothelial Cells; Engineering; Environment; Evaluation; Extracellular Fluid; Frequencies; Gases; Image; Image Analysis; Imaging Device; Imaging Techniques; In Vitro; Isotopes; Journals; Label; Lead; Legal patent; Ligands; Liposomes; Liquid substance; Localized; London; Maps; Measures; Mechanics; Medical; Medical center; Methods; Microbubbles; Microvascular Permeability; Modeling; Molecular Conformation; Monitor; Oils; Paper; Peptides; Performance; Permeability; Pharmaceutical Preparations; Pharmacology; Physiologic pulse; Physiology; Platelet Activating Factor; Positron-Emission Tomography; Principal Investigator; Property; Pulse taking; Qualifying; Radiation; Radiochemistry; Radioisotopes; Radiology Specialty; Rain; Rate; Regional Perfusion; Research; Research Personnel; Scheme; Site; Small Animal Imaging Systems; Specific qualifier value; System; Techniques; Technology; Therapeutic; Tissues; Transducers; Travel; Tumor Cell Biology; Ultrasonic Transducer; Ultrasonics; Ultrasonography; Universities; Vascular Permeabilities; Work; adhesion receptor; base; clinical application; clinically relevant; combinatorial chemistry; concept; density; design; desire; experience; image reconstruction; improved; in vivo; infancy; interest; local drug delivery; method development; nanometer; nanoparticle; novel therapeutics; oncology; particle; pressure; prototype; receptor function; response; size; submicron; targeted delivery; technique development; tomography; tool; tumor; uptake

DESCRIPTION (provided by applicant): Many promising studies indicate that ultrasound-enhanced delivery vehicles can be used to locally deliver a drug to a region of interest, with ultrasound imaging used to define the region to be treated and to monitor the inflow of the delivery vehicle. We will specifically explore the ultrasound-based mechanisms that allow new therapeutics to be concentrated in a user-specified region of interest within a tumor. These include the use of ultrasonic radiation force to increase the capture of targeted delivery agents, the release of a compound through ultrasound-induced fragmentation of the vehicle, and the use of ultrasound to mechanically or chemically induce an increase in microvascular permeability. Drug delivery vehicles can be engineered to be manipulated by ultrasonic radiation force, where the ultrasound pressure deflects the flow of the agent to the vessel wall. The vehicles can also be coated with a targeting ligand, resulting in adhesion to endothelial cells. In addition, the vehicles can be designed such that ultrasound pressure produces fragmentation of a micron-sized sphere into particles on the order of tens to hundreds of nanometers, which are taken up more readily. UC Davis and Siemens Medical Systems will create an ultrasound system and transducers that can create an image with a typical clinical frequency (2.5-7.5 MHz) and disseminate a drug to a 3D region of interest with a lower center frequency (1 MHz). A full three-dimensional integrated system will be operational in year four of the proposed work, with prototypes available earlier. Although ultrasound-enhanced local delivery has shown great promise in vitro and in preliminary in vivo studies, we believe that a system that can specify a region of interest in three dimensions and monitor the inflow of the drug vehicle must be created in order to produce reproducible and quantitative improvements. UC Davis and ImaRx will cooperate in the development and evaluation of molecularly-targeted drug delivery vehicles, with new vehicles available beginning in the first year. Additionally, in the first two years of the project period, a team of UC Davis investigators will develop PET tools required to assess the biodistribution of the labeled agents with and without insonation, and these tools will be applied throughout this project and disseminated to the imaging community. With the advent of commercially-available systems for small animal imaging with PET, the development of techniques to label drugs and drug carriers should also be of great interest. We will initially develop these drug delivery strategies for the unique environment of tumors, although the techniques should have broad application.

描述(由申请人提供)： 许多有希望的研究表明，超声增强的递送载体可以用于将药物局部递送到感兴趣的区域，并使用超声成像来确定要治疗的区域并监测递送载体的流入。我们将专门探索基于超声波的机制，允许新的治疗药物集中在肿瘤内用户指定的感兴趣区域。这些措施包括使用超声波辐射力来增加对靶向递送剂的捕获，通过超声波诱导的载体碎裂来释放化合物，以及使用超声波以机械或化学方式引起微血管通透性的增加。药物输送载体可以被设计成通过超声波辐射力来操纵，其中超声波压力将药剂的流动偏转到管壁。这种载体还可以被涂上靶向配体，从而与内皮细胞黏附。此外，这种交通工具可以被设计成超声波压力将微米大小的球体破碎成数十到数百纳米量级的颗粒，这些颗粒更容易被吸收。加州大学戴维斯分校和西门子医疗系统公司将创建一种超声系统和换能器，可以创建具有典型临床频率(2.5-7.5 MHz)的图像，并以较低的中心频率(1 MHz)将药物传播到3D感兴趣区域。一个完整的三维集成系统将在拟议工作的第四年投入使用，原型将在早些时候推出。虽然超声增强的局部递送在体外和初步的体内研究中显示出了巨大的前景，但我们认为必须创建一种系统，能够在三维上指定感兴趣的区域并监控药物载体的流入，以便产生可重复性和量化的改进。加州大学戴维斯分校和ImaRx公司将在分子靶向药物输送载体的开发和评估方面进行合作，新的载体将从第一年开始上市。此外，在项目期的头两年，加州大学戴维斯分校的一组研究人员将开发所需的PET工具，以评估在有和没有辐射的情况下标记试剂的生物分布，这些工具将在整个项目中应用，并向成像社区传播。随着商业上可用于小动物PET成像的系统的出现，标记药物和药物载体的技术的发展也应该引起极大的兴趣。我们将针对肿瘤的独特环境初步开发这些药物输送策略，尽管这些技术应该有广泛的应用。