Ultrasound imaging and local drug delivery in tumors

肿瘤中的超声成像和局部药物输送

基本信息

批准号：
8037574
负责人：
Katherine W Ferrara
金额：
$ 70.72万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-25 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8037574
关键词：
Ablation Area Biodistribution Biomedical Research Caliber Cancerous Cheek structure Chelating Agents Cherry - dietary Cisplatin Clinical Combined Modality Therapy Congresses Development Disseminated Malignant Neoplasm Dose Doxorubicin Drug Delivery Systems Drug Formulations Drug Kinetics Drug Transport Drug vehicle Encapsulated Faculty Fever Fluoroscopy Goals Grant Gray unit of radiation dose Growth Hamsters Head and Neck Cancer Head and Neck Neoplasms Head and neck structure Heating Hour Human Image Imagery In Vitro Individual Induced Hyperthermia Injection of therapeutic agent Intervention Intravenous Journals Label Laboratories Lateral Lesion Liposomes Malignant Neoplasms Mammary Neoplasms Maps Mechanics Mediating Medical Metastatic Lesion Methods Modeling Molecular Nanotechnology Neoplasm Metastasis Optical Tomography Optics Oryctolagus cuniculus Osmolar Concentration Paper Pattern Pharmaceutical Preparations Pharmacotherapy Positioning Attribute Positron-Emission Tomography Postdoctoral Fellow Primary Neoplasm Prostatic Neoplasms Protocols documentation Publishing Quality of life Recruitment Activity Reporting Research Infrastructure Research Personnel Scanning Solutions Students System Systemic Therapy Techniques Temperature Testing Therapeutic Time Tissues Toxic effect Transducers Translations Treatment Efficacy Ultrasonic Therapy Ultrasonics Ultrasonography United States Universities Validation Width X-Ray Computed Tomography base cancer imaging cancer therapy chelation chemotherapy image guided intervention imaging modality imaging probe improved in vivo interest intravenous injection local drug delivery malignant breast neoplasm melanoma member multimodality nanoparticle oncology optical imaging palliation particle preclinical study pressure professor response symposium translational study tumor

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this biomedical research partnership is to couple cancer imaging and therapy using nanoparticles that provide ultrasonic activation, multimodality imaging, and efficient and stable drug transport. These methods enable efficacious drug delivery with minimal systemic toxicity in the treatment of multifocal and metastatic cancers, and in particular in melanoma, head and neck, prostate, and breast tumors. There is great momentum for image-guided interventions in general and image-guided drug delivery in particular, with many activatable particles under development. In our first grant cycle, we established the feasibility of ultrasound drug delivery to tumors, demonstrating that we can: target a significant fraction of drug carrying particles to tumors (averaging 20% of the injected dose per cubic centimeter of tissue following systemic administration), obtain a high (up to 33 dB) target-to-background ratio image of the vehicles within the cancerous lesion, image tumors with a diameter of 4 mm or greater, achieve at least a 50-fold increase in drug delivery to tumors (as compared with systemic administration of free model drugs), and demonstrate a therapeutic response in vivo with the combination of ultrasound and liposomal cisplatin in as little as 24 hours. We have also created ultrasound infrastructure for imaging and therapy, embedding therapeutic capabilities within the clinical ultrasound system of our partner Siemens Medical Solutions, creating a positron emission tomography (PET) labeling method for liposomes, synthesizing a near-infrared probe, and cross-validating these components. Our ultrasound imaging and therapy system can operate independently or in combination with PET and computed tomography (CT). The primary goal for this renewal is to establish efficacious infrastructure and protocols for ultrasound-enhanced particle-based drug delivery for the treatment of primary and metastatic tumors. In order to accomplish this goal we will create a combined PET-CT-US system for image-guided-interventions, optimize the 3D-ultrasound heating protocol, maximize the target-to-background ratio for guiding interventions with PET-CT-US, finalize the loading and formulation for an activatable cisplatin liposome and evaluate ultrasound-enhanced intravenous therapy under PET-CT guidance.

描述（由申请人提供）：这种生物医学研究伙伴关系的总体目标是使用提供超声激活，多模式成像以及高效且稳定的药物运输的纳米颗粒进行癌症成像和治疗。这些方法在治疗多焦点和转移性癌症方面，尤其是黑色素瘤，头颈，前列腺和乳腺肿瘤，具有最小的全身毒性，可以有效地输送药物。通常，图像引导的干预措施尤其是图像引导的干预措施，特别是图像引导的药物输送，许多可激活的颗粒正在开发中。在我们的第一个赠款周期中，我们确定了超声药物向肿瘤递送的可行性，表明我们可以：靶向大量的携带颗粒的药物携带到肿瘤的药物（全身给药后，每个立方体的组织的注射剂量的20％），获得高（最高33 db）目标的疾病图像的较高（最高33 dB）的癌症图像，该图像较大的疾病图像，均匀均匀的疾病图像，均匀的疾病图像，图像较大的一位图像，图像较大，图像较大的图像，图像较大，图像较大的图像，图像较大的图像，图像较大的图像，图像较大的图像，图像较大的图像，图像较大的图像，图像较大的图像，图像较大的图像，图像较大的图像，图像是MMM的图像。至少增加了50倍的药物向肿瘤递送（与全身施用自由模型药物相比），并在24小时内与超声和脂质体顺铂结合结合了体内的治疗反应。我们还创建了用于影像学和治疗的超声基础设施，将治疗能力嵌入我们伴侣西门子医疗解决方案的临床超声系统中，从而为脂质体创建了正电子发射断层扫描方法（PET）标记方法，用于平原型近红外探针，并交叉估算这些组合。我们的超声成像和治疗系统可以独立运行，也可以与PET和计算机断层扫描（CT）结合使用。这种更新的主要目的是建立有效的基础设施和基于颗粒的药物递送的基础设施和方案，以治疗原发性和转移性肿瘤。 In order to accomplish this goal we will create a combined PET-CT-US system for image-guided-interventions, optimize the 3D-ultrasound heating protocol, maximize the target-to-background ratio for guiding interventions with PET-CT-US, finalize the loading and formulation for an activatable cisplatin liposome and evaluate ultrasound-enhanced intravenous therapy under PET-CT guidance.