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.

项目概述：本提案描述了一个为期五年的研究和职业发展计划的准备