Precision magnetic hyperthermia by integrating magnetic particle imaging

通过集成磁粒子成像实现精确磁热疗

• 批准号: 10415219
• 负责人: Jeff W. Bulte
• 金额: $ 61.54万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10415219
• 关键词: 3-Dimensional; Algorithms; Animal Model; Animals; Biological; Biomedical Research; Breast Cancer Model; Clinical; Clinical Trials; Colloids; Computer Models; Computer software; Contrast Media; Diagnosis; ERBB2 gene; Effectiveness; Emerging Technologies; European; Fiber Optics; Funding; Gel; Glioblastoma; Grant; Heating; Histology; Human; Hyperthermia; Image; Imaging technology; Liver; Location; Magnetic Resonance Imaging; Magnetic fluid hyperthermia; Magnetic nanoparticles; Magnetism; Malignant Neoplasms; Malignant neoplasm of prostate; Mammary Neoplasms; Measurement; Metastatic Neoplasm to the Lung; Metastatic breast cancer; Methods; Modeling; Mus; Nanotechnology; Normal tissue morphology; Physiologic pulse; Positioning Attribute; Property; Radiation therapy; Rattus; Recurrence; Relaxation; Research Personnel; Resistance; Resolution; Sampling; Signal Transduction; Suspensions; System; Technology; Temperature; Testing; Therapeutic; Therapeutic Effect; Thermometry; Time; Tissues; Toxic effect; Tracer; Transgenic Organisms; Treatment Efficacy; Tumor Burden; Validation; Width; base; cancer therapy; candidate selection; clinical application; clinically relevant; contrast enhanced; detection sensitivity; hyperthermia treatment; image guided; in vivo; instrumentation; iron oxide nanoparticle; magnetic field; nanotheranostics; particle; pre-clinical; rectal; sensor; technology development; theranostics; treatment planning; tumor; tumor growth

Precision magnetic hyperthermia by integrating magnetic particle imaging Magnetic activation of magnetic iron oxide nanoparticles (MIONPs) offers considerable potential for numerous biomedical applications. Approved clinical applications include contrast enhancement for magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH) for cancer treatment. MIONPs are T2 negative contrast agents which have been clinically available for MRI since the late 1980s where very low tissue concentrations (<100 g Fe/g tissue) are needed for imaging. MFH is a powerful nanotechnology-based treatment that enhances radiation therapy (RT). It comprises local heating of tissue by activating MIONPs with an external alternating magnetic field (AMF), enabling treatment anywhere in the body. Human clinical trials demonstrated benefits of MFH for prostate cancer; and, overall survival benefits with RT in recurrent glioblastoma (GBM) resulted in European approval in 2010. However, current MFH effectiveness is limited by the inability to visualize MIONP distribution during MFH, resulting in poor AMF control of MIONP heating, reduced therapeutic efficacy, and unwanted off-target toxicity. An integrated MIONP imaging-MFH technology that provides spatial control of the MFH treatment volume will substantially advance the clinical use of theranostic MIONPs. Magnetic particle imaging (MPI) is an emerging imaging technology that directly quantitates MIONP concentration in tissue with similar or greater sensitivity as MRI. The main magnet in an MPI scanner produces a strong magnetic field gradient containing a region where the magnetic field is approximately zero, i.e. the Field Free Region (FFR). MIONPs in the FFR are magnetically unsaturated and can produce a signal in a receiver coil, while MIONPs elsewhere are magnetically saturated and produce no signal. Images are produced by rastering the FFR across the sample. The FFR used for imaging can be used to localize MFH. By applying a magnetic field gradient and AMF, only MIONPs inside the FFR will heat while MIONPs outside the FFR are saturated and do not heat. MPI and MFH are compatible enabling mm-precision spatial control of MFH. Our objective is to develop an integrated MPI/MFH workflow that incorporates imaging-guided treatment planning with optimal theranostic MIONPs for preclinical biomedical research with small animal (mouse and rat) models. We aim to achieve our objectives by purchasing a HYPER AMF system that will be used with our recently acquired Momentum MPI scanner (funded by a S10 shared instrumentation grant). Our specific aims are: (Aim 1) Identify MIONPs having ideal physical and magnetic properties for MPI/MFH; (Aim 2) Develop MPI-guided MFH treatment using computational modeling and amplitude modulation; (Aim 3) Demonstrate increased therapeutic efficacy of theranostic MPI/MFH in vivo. While the primary objective of the proposed effort is technology development, successful completion of the aims will provide biomedical researchers the ability to realize theranostic applications with magnetic nanoparticles.

通过集成磁粒子成像实现精确磁热疗 磁性氧化铁纳米颗粒 (MIONP) 的磁活化为众多领域提供了巨大的潜力 生物医学应用。批准的临床应用包括磁共振对比增强 用于癌症治疗的成像（MRI）和磁流体热疗（MFH）。 MIONP 是 T2 负对比 自 20 世纪 80 年代末以来临床上可用于 MRI 的药物，其组织浓度非常低 （<100 µg Fe/g 组织）用于成像。 MFH 是一种基于纳米技术的强大治疗方法，可增强 放射治疗（RT）。它包括通过外部交流电激活 MIONP 来局部加热组织 磁场 (AMF)，可在身体任何部位进行治疗。人体临床试验证明了其益处 MFH 治疗前列腺癌；并且，放疗对复发性胶质母细胞瘤 (GBM) 的总体生存获益 欧洲于 2010 年获得批准。然而，目前 MFH 的有效性因无法可视化 MIONP 而受到限制 MFH期间的分布，导致AMF对MIONP加热的控制不佳，降低治疗效果，并且 不需要的脱靶毒性。集成的 MIONP 成像-MFH 技术，可提供空间控制 MFH 治疗量将大大推进治疗诊断 MIONP 的临床应用。磁粉 成像（MPI）是一种新兴的成像技术，可直接定量组织中的 MIONP 浓度 similar or greater sensitivity as MRI. MPI 扫描仪中的主磁体产生强磁场 包含磁场近似为零的区域的梯度，即无场区域（FFR）。 FFR 中的 MIONP 磁性不饱和，可以在接收器线圈中产生信号，而 MIONP 其他地方磁饱和并且不产生信号。图像是通过对 FFR 进行光栅化生成的 样品。用于成像的 FFR 可用于定位 MFH。通过施加磁场梯度和 AMF，只有 FFR 内部的 MIONP 会加热，而 FFR 外部的 MIONP 已饱和，不会加热。 MPI 和 MFH 兼容，可实现 MFH 的毫米级精度空间控制。我们的目标是开发一个集成的 MPI/MFH 工作流程将影像引导治疗计划与最佳治疗诊断 MIONP 相结合，用于 使用小动物（小鼠和大鼠）模型进行临床前生物医学研究。我们旨在通过以下方式实现我们的目标 购买 HYPER AMF 系统，该系统将与我们最近购买的 Momentum MPI 扫描仪（资助 通过 S10 共享仪器补助）。我们的具体目标是：（目标 1）识别具有理想身体素质的 MIONP 以及 MPI/MFH 的磁特性； （目标 2）利用计算开发 MPI 引导的 MFH 治疗 建模和幅度调制； （目标 3）证明治疗诊断的治疗效果提高 体内 MPI/MFH。虽然拟议工作的主要目标是技术开发，但成功 目标的完成将为生物医学研究人员提供实现治疗诊断应用的能力 磁性纳米颗粒。