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)

基本信息

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
项目类别：
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

项目摘要

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：该提案描述了一个为期五年的研究和职业发展计划，以准备哈米德·阿拉米 (Hamed Arami) 博士作为独立调查员的职业生涯该计划将建立在阿拉米 (Arami) 博士的基础上。具有多学科背景的生物工程科学家，接受过纳米医学和基础癌症成像方面的培训，提供脑癌生物学和使用磁粒子图像引导脑肿瘤治疗的专业知识成像（MPI）。 PI 将由 Sanjiv S. Gambhir 博士（主要导师，基础癌症生物学、癌症病理学和癌症纳米技术），Heike Daldrup-Link（共同导师，磁性 Max Wintermark（联合导师，神经影像学和大脑 MPI），Melanie Hayden（共同导师，神经外科和神经病学）和 Bob Sinclair（共同导师，纳米材料表征）。恶性原发性脑肿瘤，特别是多形性胶质母细胞瘤（GBM）的治疗具有挑战性，因为 GBM 肿瘤对化疗和放疗具有耐药性。此外，还有不同类型的 GBM 肿瘤不耐受化疗和放疗。由于它们在大脑中的位置（例如大脑深部区域），因此可以进行操作。此外，临床中的常规 GBM 成像。是基于使用钆基磁共振成像造影剂然而，使用这些。钆基造影剂引起了患有慢性肾病的 GBM 患者的主要担忧疾病，可以通过使用纳米颗粒造影剂来解决，由于纳米颗粒造影剂不显示任何肾脏清除率拟议研究的总体目标是将 MPI 用作双臂和高分辨率。四种不同类型脑肿瘤的更安全成像和磁热治疗方法。将研究攻击性水平，以确定所提出的方法在不同脑肿瘤中的可行性最近，我开发了调节氧化铁纳米粒子（NP）以产生高浓度的方法。分辨率（即 ~600 µm）MPI 图像，具有低于 ~550pg Fe/µL 的超高造影剂质量灵敏度。我曾使用MPI对小鼠U87脑肿瘤静脉注射后进行三维靶向成像此外，在单独的研究中，我证明了 MPI 选择性的可行性。当纳米粒子直接注射到肿瘤中时，U87 肿瘤的磁热疗法。首先评估不同脑深度的NPs的MPI和产热效率，以进一步理想地识别NPs 一般脑肿瘤成像或 MPI 局部磁热治疗的设计和成像标准（目标 1）。然后，我将评估 MPI 对四种不同类型颅内植入脑肿瘤的靶向 3D 成像静脉注射纳米颗粒后，进行纳米颗粒生物分布研究（目标 2）。我将使用瘤内注射我的肿瘤穿透纳米粒子来进行 MPI 引导的深部磁热治疗脑肿瘤（无法手术的 GBM 的代表性模型），然后是深入的生存和神经病理学研究（目标 3）：氧化铁纳米颗粒已获得 FDA 批准用于多项临床应用，我们希望这种方法最终能够应用于许多其他类型的实体瘤。