Quantitative MRI-Guided Nanoembolization for Liver Cancer

定量 MRI 引导的肝癌纳米栓塞术

• 批准号: 8320165
• 负责人: Andrew Christian Larson
• 金额: $ 48.64万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8320165
• 关键词: Address; Animals; Biodistribution; Biomedical Engineering; Body Surface Area; Catheters; Chemistry; Chemoembolization; Clinical; Dose; Doxorubicin; Drug Delivery Systems; Drug usage; Eligibility Determination; Ensure; Feedback; Fluoroscopy; Future; Goals; Gold; Health; Image; Imaging Techniques; Interventional radiology; Intravenous; Liver; Liver neoplasms; Local Therapy; Magnetic Resonance Imaging; Malignant neoplasm of liver; Maps; Methods; Modeling; Monitor; Nanotechnology; Organ; Oryctolagus cuniculus; Outcome; Oxides; Patients; Perfusion; Pharmaceutical Preparations; Primary carcinoma of the liver cells; Procedures; Property; Protocols documentation; Radiation Oncologist; Radiation therapy; Radiometry; Regimen; Research Personnel; Reticuloendothelial System; Series; Solid; System; Techniques; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Toxic effect; Translating; Translations; Unresectable; Weight; advanced disease; base; cancer therapy; chemotherapy; dosimetry; imaging modality; imaging probe; improved; indexing; innovation; intravenous administration; iron oxide; liver function; meetings; nanoparticle; nanotherapy; next generation; novel strategies; outcome forecast; radiologist; success; tumor; tumor vascular supply; uptake

DESCRIPTION (provided by applicant): The broad, long-term objective of this proposal is to improve the prognosis of patients with unresectable hepatocellular carcinoma (HCC). For these patients, transarterial chemoembolization (TACE) is the most widely accepted local treatment because of its proven survival benefit in patients with preserved liver function. However, benefit to patients with advanced disease or poor liver function is still limited. The optimal dose for TACE also remains unknown. To address the need to expand patient eligibility and optimize dosing protocols for TACE, the investigators propose: a) developing the next generation of TACE by using nanoparticles (NP) as drug delivery vehicles for doxorubicin (DOX) and b) devising a new magnetic resonance imaging (MRI) system to predict and monitor dosimetry for this locally delivered therapy. The proposed improvement to TACE employs therapeutic nanoparticles (NP) in a new procedure termed nanoembolization (NE). NE is local delivery of therapeutic NPs, together with embolic agents, into the tumor blood supply to increase intratumoral drug uptake. The investigators' NP platform employs a central superparamagnetic oxide (SPIO) core that can be imaged with MRI, enclosed within a gold (Au) shell that is attached to DOX as the therapeutic agent. The proposal will test the utility of an MRI-monitoring system for delivery of Au-SPIOs in the VX2 rabbit model of HCC. This system will enable prediction of dosimetry prior to drug delivery, real-time monitoring during drug delivery, and feedback after delivery to verify that desired intratumoral drug concentrations have been reached. Specific Aim 1 will develop a model that predicts tissue concentrations of Au-SPIOs before delivery and provides imaging parameters for dosimetry. It is hypothesized that quantitative MRI parameters can be used to predict the biodistribution of injected Au-SPIOs before delivery and to provide dosimetry for NE. The health relevance will be to personalize liver tumor therapies for patients based upon local tumor perfusion. Specific Aim 2 will develop a real-time projection MRI fluoroscopy technique that can monitor Au-SPIO delivery in real- time during NE. It is hypothesized that Au-SPIO delivery during NE can be monitored in real-time with dynamic projection MRI. The health relevance is to develop a real-time imaging method that ensures injected NPs reach their intended tumor target. Specific Aim 3 will use MRI to quantify tissue concentrations of Au-SPIOs after NE. It is hypothesized that MRI R2* mapping accurately quantifies tissue concentrations of Au-SPIOs after NE. The health relevance is to provide quantitative intra-procedural feedback during drug delivery, with the goal of maximizing intratumoral drug concentrations, while minimizing toxicity to adjacent liver tissue.

描述（由申请人提供）：该提案的广泛长期目标是改善无法切除的肝细胞癌（HCC）患者的预后。对于这些患者，跨性化学栓塞（TACE）是最广泛接受的局部治疗，因为它在保留的肝功能的患者中已证明其生存率。但是，对患有晚期疾病或肝功能不佳的患者的好处仍然有限。 TACE的最佳剂量也是未知的。为了满足扩大患者资格并优化TACE的剂量方案的需求，研究人员建议：）提出：）通过使用纳米颗粒（NP）作为阿霉素（DOX）（dox）和b）设计下一代TACE，并设计了一种新的磁共振成像（MRI）系统来预测和监视此处提供的dosimetry。拟议的改进对TACE采用了治疗性纳米颗粒（NP），以称为纳米栓塞（NE）的新程序。 NE是治疗性NP的局部递送，以及栓塞剂，进入肿瘤血液供应，以增加肿瘤内药物的摄取。研究人员的NP平台采用了中央的超帕磁化氧化物（SPIO）核心，可以用MRI成像，该核心封闭在金（AU）壳中，该壳与DOX连接为治疗剂。该提案将测试MRI监控系统在HCC的VX2兔模型中传递Au-Spios的实用性。该系统将在药物输送之前预测剂量法，药物输送期间的实时监测以及输送后的反馈，以验证已达到所需的肿瘤内药物浓度。特定的目标1将开发一个模型，该模型在分娩前预测Au-Spios的组织浓度，并为剂量测定法提供成像参数。假设定量MRI参数可用于预测注射的Au-Spios的生物分布，并为NE提供剂量测定法。健康相关性是根据局部肿瘤灌注来个性化患者的肝肿瘤疗法。特定的目标2将开发一种实时投影MRI荧光镜检查技术，该技术可以在NE期间实时监测AU-Spio的交付。假设可以使用动态投影MRI实时监测NE期间的Au-Spio递送。健康相关性是开发一种实时成像方法，以确保注射的NP达到预期的肿瘤靶标。特定的目标3将使用MRI来定量NE后Au-Spios的组织浓度。假设MRI R2*映射可以准确量化NE后的Au-Spios的组织浓度。健康相关性是在药物输送过程中提供定量的肠内反馈，目的是最大化肿瘤内药物浓度，同时最大程度地减少对邻近肝组织的毒性。