Magnetic Particle Imaging (MPI) for Imaging and Magnetothermal Therapy of Brain Tumors

用于脑肿瘤成像和磁热治疗的磁粒子成像 (MPI)

• 批准号: 9891731
• 负责人: Hamed Arami
• 金额: $ 15.45万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891731
• 关键词: 3-Dimensional; Adjuvant; Animal Model; Autopsy; Biodistribution; Biological; Biomedical Engineering; Blood - brain barrier anatomy; Brain; Brain Glioblastoma; Brain Neoplasms; Brain region; Cancer Biology; Chemotherapy and/or radiation; Chlorotoxin; Chronic Kidney Failure; Clinic; Contrast Media; Data; Dose; Excision; FDA approved; Focused Ultrasound Therapy; Gadolinium; Generations; Glioblastoma; Goals; Growth; Heating; Human; Image; Imaging Device; Imaging Techniques; Implant; Injections; Iron; Knowledge; Link; Liver; Location; Lung; Magnetic Resonance Imaging; Magnetic nanoparticles; Magnetism; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of brain; Mentors; Methods; Modeling; Monitor; Mus; Nanotechnology; Neurology; Operative Surgical Procedures; Organ; Ovarian; Pancreas; Pathology; Patients; Peptides; Positron-Emission Tomography; Primary Brain Neoplasms; Program Development; Property; Prostate; Publishing; Radiation therapy; Recurrence; Relaxation; Renal clearance function; Research; Research Personnel; Resistance; Resolution; Safety; Scientist; Signal Transduction; Site; Solid Neoplasm; Spleen; Survival Rate; Techniques; Therapeutic; Three-Dimensional Imaging; Tissues; Training; Tumor Cell Line; Tumor Tissue; Unresectable; base; bioimaging; biomaterial compatibility; brain tissue; brain tumor imaging; cancer imaging; career; career development; chemotherapy; clinical application; contrast imaging; cost effective; design; dosage; experience; high resolution imaging; image guided; image guided therapy; imaging study; implantation; improved; intravenous administration; intravenous injection; iron oxide nanoparticle; medical schools; mortality; multidisciplinary; nanomaterials; nanomedicine; nanoparticle; neural implant; neuroimaging; neurosurgery; novel; particle; programs; radioresistant; radiotracer; research and development; response; subcutaneous; superparamagnetism; targeted imaging; tool; tumor; tumor ablation; tumor microenvironment; tumor xenograft; uptake

Project Summary: This proposal describes a five-year research and career development program to prepare Dr. Hamed Arami for a career as an independent investigator. This program will build upon Dr. Arami’s multidisciplinary background as a bioengineer scientist, trained in nanomedicine and basic cancer imaging, by providing expertise in brain cancer biology and image-guided therapy of brain tumors using Magnetic Particle Imaging (MPI). The PI will be mentored at Stanford Medical School by Drs. Sanjiv S. Gambhir (Main mentor, basic cancer biology, cancer pathology and cancer nanotechnology), Heike Daldrup-Link (co-mentor, magnetic nanomedicine, imaging and therapeutics), Max Wintermark (co-mentor, neuroimaging and brain MPI), Melanie Hayden (co-mentor, neurosurgery and neurology) and Bob Sinclair (co-mentor, nanomaterials characterization). Treatment of malignant primary brain tumors particularly glioblastoma multiforme (GBM) is challenging because of GBM resistant to chemotherapy and radiotherapy. Also, there are different types of GBM tumors that are not operable due to their locations in the brain (e.g. deep brain regions). In addition, routine GBM imaging in clinics are based on using gadolinium-based magnetic resonance imaging contrast agents. However, using these gadolinium-based contrast agents raises major concerns for GBM patients suffering from chronic kidney disease, which can be resolved by using nanoparticle contrast agents that do not show any renal clearance due to their larger size. The overall goal of the proposed research is to use MPI as a two-armed and high-resolution approach for safer imaging and magnetothermal therapy of the GBM. Four types of brain tumors with different levels of aggressiveness will be studied to identify the feasibility of the proposed method in different brain tumor microenvironments. Recently, I developed methods for tuning iron oxide nanoparticles (NPs) to generate high resolution (i.e. ~600 µm) MPI images with ultra-high contrast agent mass sensitivity of less than ~550pg Fe/µL. I have used MPI for three-dimensional targeted imaging of the U87 brain tumors in mice after intravenous injection of these NPs. Additionally, in separate studies, I demonstrated the feasibility of the MPI for selective magnetothermal therapy of the U87 tumors, when NPs were directly injected into tumors. In this project, I will first evaluate MPI and heat generation efficiency of the NPs at different brain depths to further identify ideal NPs design and imaging criteria for general brain tumor imaging or local magnetothermal therapy with MPI (Aim 1). Then, I will evaluate MPI for targeted 3D imaging of four different types of intracranially implanted brain tumors after intravenous injection of the nanoparticles, followed by nanoparticle biodistribution studies (Aim 2). Finally, I will use intratumoral injection of my tumor-penetrating NPs for MPI-guided magnetothermal therapy of the deep brain tumors (representative models for inoperable GBM), followed by in-depth survival and neuropathological studies (Aim 3). Iron oxide nanoparticles have been approved by FDA for several clinical applications and we hope that this method will ultimately find applications to many other types of solid tumors.

项目摘要：该提案描述了一项为期五年的研究和职业发展计划 Hamed Arami博士从事独立调查员的职业。该计划将以Arami博士为基础 作为生物工程学的多学科背景，通过纳米医学和基本癌症成像培训 使用磁性粒子提供脑癌生物学和图像引导治疗的专业知识 成像（MPI）。 PI将由Drs在斯坦福医学院指导。 Sanjiv S. Gambhir（主要导师， 基本癌症生物学，癌症病理学和癌症纳米技术），Heike Daldrup-Link（磁性，磁 纳米医学，成像和治疗），最大冬季标记（Co-Contor，神经影像和脑MPI），梅兰妮 海登（神经外科和神经病学）和鲍勃·辛克莱（Bob Sinclair）（纳米材料表征）。 尤其是多形胶质母细胞瘤（GBM）的恶性原发性脑肿瘤的治疗是具有挑战性的，因为 GBM对化学疗法和放疗的抗性。另外，有不同类型的GBM肿瘤不是 由于它们在大脑中的位置（例如深脑区域），可操作。此外，诊所的常规GBM成像 基于使用基于Gadolinium的磁共振成像对比剂。但是，使用这些 基于Gadolinium的对比剂引起了对患有慢性肾脏的GBM患者的主要关注点 疾病，可以通过使用未显示任何肾脏清除率的纳米颗粒对比剂来解决的疾病 达到更大的尺寸。拟议的研究的总体目标是将MPI用作两臂和高分辨率 GBM的安全成像和磁化疗法的方法。四种类型的脑肿瘤不同 将研究侵略性水平，以确定所提出方法在不同脑肿瘤中的可行性 微环境。最近，我开发了调谐氧化铁纳米颗粒（NP）的方法 分辨率（即〜600 µm）MPI图像具有超高对比剂质量灵敏度小于550pg fe/µl。 我已经使用MPI进行了静脉内U87脑肿瘤的三维靶向成像 注入这些NP。此外，在单独的研究中，我证明了MPI对选择性的可行性 当NP直接注入肿瘤时，U87肿瘤的磁热疗法。在这个项目中，我会 首先评估NP在不同大脑深度的MPI和热量产生效率，以进一步识别理想的NP 使用MPI的一般脑肿瘤成像或局部磁性治疗的设计和成像标准（AIM 1）。 然后，我将评估MPI的靶向3D成像的四种不同类型的颅内植入脑肿瘤的成像 静脉注射纳米颗粒后，然后进行纳米颗粒生物分布研究（AIM 2）。最后， 我将使用肿瘤内注射我的肿瘤穿透NPS进行MPI引导的磁热疗法 脑肿瘤（无法手术GBM的代表性模型），其次是深入生存和神经病理学 研究（目标3）。 FDA已批准了氧化铁纳米颗粒用于多种临床应用，我们 希望这种方法最终会在许多其他类型的实体瘤中找到应用。