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: 10667448
• 负责人: Jeff W. Bulte
• 金额: $ 63.6万
• 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/10667448
• 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; Rectum; 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; Visualization; Width; cancer therapy; candidate selection; clinical application; clinically relevant; contrast enhanced; detection sensitivity; hyperthermia treatment; image guided; in vivo; instrumentation; iron oxide; iron oxide nanoparticle; magnetic field; nanoparticle; nanoparticle delivery; nanotheranostics; optical fiber; particle; pre-clinical; rectal; sensor; technology development; theranostics; treatment planning; tumor; tumor growth; zeta potential

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.

通过整合磁性粒子成像，精确磁热热 磁氧化铁纳米颗粒（MIONPS）的磁激活为众多的考虑潜力 生物医学应用。批准的临床应用包括磁共振的对比度增强 成像（MRI）和磁性流体高温（MFH）进行癌症治疗。 MIONPS是T2负面对比度 自1980年代后期以来一直在临床上可用于MRI的药物，该组织非常低的组织浓度 成像需要（<100gFe/g组织）。 MFH是一种强大的基于纳米技术的治疗方法，可增强 放射疗法（RT）。它通过用外部替代方案激活Mionp来包括组织的局部加热 磁场（AMF），可以在体内任何地方进行治疗。人类临床试验表明了 MFH前列腺癌；并且，RT在复发性胶质母细胞瘤（GBM）中的总体生存益处导致 但是，2010年的欧洲批准。但是，当前的MFH有效性受到无法可视化Mionp的限制 MFH期间的分布，导致对MIONP加热的AMF控制不佳，治疗效率降低和 不需要的脱靶毒性。一种集成的MIONP成像MFH技术，可提供空间控制 MFH治疗量将大大提高疗法MIONP的临床使用。磁性粒子 成像（MPI）是一种新兴的成像技术，可以直接量化组织中的MIONP浓度 与MRI相似或更高的灵敏度。 MPI扫描仪中的主磁铁产生强磁场 梯度包含磁场约为零的区域，即无磁场区域（FFR）。 FFR中的MIONPS磁不饱和，可以在接收器线圈中产生信号，而Mionps 其他地方是磁性饱和的，没有信号。图像是通过将FFR栅栏横冲直撞而产生的 样本。用于成像的FFR可用于定位MFH。通过应用磁场梯度和 AMF，只有FFR内部的MIONP会加热，而FFR以外的MIONP饱和并且不加热。 MPI MFH和MFH兼容MM精确的MFH空间控制。我们的目标是开发一个综合的 MPI/MFH工作流程将成像引导的治疗计划与最佳的Theranotic Mionps合并 小动物（小鼠和大鼠）模型的临床前生物医学研究。我们旨在通过 购买将与我们最近获得的动量MPI扫描仪一起使用的超级AMF系统（资助 由S10共享仪器赠款）。我们的具体目的是：（目标1）确定具有理想物理的Mionp MPI/MFH的磁性特性； （AIM 2）使用计算开发MPI引导的MFH治疗 建模和振幅调制； （AIM 3）证明疗法的治疗效率提高 MPI/MFH体内。虽然拟议的努力的主要目标是技术发展，但成功 目的的完成将为生物医学研究人员提供实现治疗应用的能力 磁性纳米颗粒。