Development of a prototype clinical theranostic platform combining Magnetic Particle Imaging (MPI) and Magnetic Fluid Hyperthermia (MFH) for the treatment of brain tumors

开发结合磁粒子成像（MPI）和磁流体热疗（MFH）的原型临床治疗平台，用于治疗脑肿瘤

• 批准号: 10761630
• 负责人: Patrick Goodwill
• 金额: $ 101.17万
• 依托单位: MAGNETIC INSIGHT, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10761630
• 关键词: 3-Dimensional; Abscopal effect; Animals; Applications Grants; Area; Brain Neoplasms; Cadaver; Cancer Model; Canis familiaris; Cell Death; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Computer software; Data; Development; Devices; Diagnostic Imaging; Dose; Effectiveness; Engineering; Europe; European; Feedback; Future; Glioblastoma; Goals; Grant; Head; Heating; Human; Image; Imaging technology; Immune response; Immunologic Stimulation; In Vitro; Intensity-Modulated Radiotherapy; Lesion; Magnetic fluid hyperthermia; Magnetic nanoparticles; Magnetism; Malignant neoplasm of prostate; Measurement; Measures; Modeling; Monitor; Normal tissue morphology; Oils; Penetration; Performance; Phase; Preparation; Radiation therapy; Radio; Recurrence; Resolution; Scanning; Shapes; Signal Transduction; Small Business Innovation Research Grant; System; Technology; Temperature; Temperature Sense; Testing; Therapeutic; Therapeutic Effect; Time; Tissues; Universities; Visualization; Water; Width; Work; attenuation; brain size; cancer therapy; chemotherapy; clinical imaging; commercialization; cytotoxic; design; dosimetry; experience; hyperthermia treatment; image guided; imager; imaging system; immunogenic cell death; in vivo; in vivo Model; innovation; insight; interest; magnetic field; millimeter; nanoparticle; neoplastic cell; new technology; particle; pre-clinical; preclinical trial; prototype; quality assurance; theranostics; time use; tomography; treatment planning; tumor

SUMMARY/ABSTRACT In this SBIR grant proposal, “Development of a prototype clinical theranostic platform combining Magnetic Particle Imaging (MPI) and Magnetic Fluid Hyperthermia (MFH) for the treatment of brain tumors” we will develop a human brain-sized, integrated localized MFH/MPI system. We will develop an imaging-guided MFH treatment device capable of closed-loop localized heating and tomographic temperature monitoring during treatment. MFH relies on the delivery of magnetic nanoparticles to tumors followed by application of alternating magnetic fields, which causing local heating of tissue and killing of tumor cells. Cell death occurs due to the heat or by enhancing the cytotoxic effects of radio/chemotherapy. MFH offers considerable potential for numerous biomedical applications, especially as an adjunct to radiation therapy in the clinical treatment of recurrent glioblastoma. However, MFH currently suffers from limitations that persist after nearly four decades of clinical experience and regulatory approval in Europe. Following delivery, the nanoparticle distribution within the tumor can be heterogeneous and unpredictable, leading to undertreatment in areas of low MNP concentration, and excessive heating near normal tissues. These issues are compounded by a limited ability to accurately monitor tissue temperature in 3D and in realtime. The technology developed in this SBIR constitutes a paradigm shift for MFH by developing the first human- sized localized MFH system. Localized MFH is a new technology that uses strong magnetic field gradients to confine MNP heating to a small region. Particles within the region can generate heat, while those outside the region cannot. Our technology will transition clinical MFH from the current state of the art of loosely targeted, regional heating to mm-accurate localized heating of target tissues. We believe this transition from regional to precisely targeted is comparable to the transition of early, loosely targeted radiation therapy to the present day, 3D-targeted intensity-modulated radiation therapy. In this Direct to Phase II SBIR proposal, we will add MFH to our existing clinical-scale MPI prototype to enable localized MPI/MFH with integrated temperature sensing, and validate the performance in animal cadavers through the following specific aims: Aim 1. Build a clinical RF heating head coil for simultaneous MFH and imaging and integrate it into our prototype clinical imager Aim 2. Integrate MPI-based temperature sensing with heating to control MFH to a treatment plan. Aim 3. Test overall system in phantoms and animal cadavers in preparation for preclinical trials in dogs At the end of this Direct to Phase II proposal, we will have demonstrated integrated MPI/MFH for precisely localized image-guided therapeutic heating in a prototype that is suitable for clinical studies. In our future work, we plan to test this system in a large animal trial at JHU for treatment of spontaneous canine GBM.

总结/摘要 在这项SBIR拨款提案中，“开发一种结合磁共振成像的原型临床治疗诊断平台”， 粒子成像（MPI）和磁流体热疗（MFH）治疗脑肿瘤”我们将开发 人脑大小的集成局部MFH/MPI系统。我们将开发一种成像引导的MFH治疗方法， 能够在治疗期间进行闭环局部加热和断层扫描温度监测的器械。 MFH依赖于将磁性纳米颗粒递送到肿瘤，然后施加交变磁性纳米颗粒。 场，其引起组织的局部加热和肿瘤细胞的杀伤。细胞死亡是由于热或 增强放疗/化疗的细胞毒效应。MFH为众多 生物医学应用，特别是作为放射治疗的辅助手段，用于临床治疗复发性 胶质母细胞瘤然而，MFH目前受到在近四十年的临床应用后仍然存在的局限性的影响。 在欧洲的经验和监管批准。递送后，肿瘤内的纳米颗粒分布 可能是异质的和不可预测的，导致自然流动人口低浓度地区的治疗不足， 正常组织附近的过热。这些问题因准确监测能力有限而变得更加复杂 组织温度的3D和实时。 该SBIR中开发的技术通过开发第一个人类- 国产化MFH系统。局部MFH是一种新技术，它使用强磁场梯度， 将MNP加热限制在小区域内。区域内的粒子可以产生热量，而区域外的粒子可以产生热量。 地区不能。我们的技术将使临床MFH从目前的松散靶向， 局部加热到靶组织的毫米级精确局部加热。我们认为，这种从区域到 精确靶向与早期的、松散靶向的放射治疗到今天的过渡相当， 3D靶向调强放射治疗。 在这个直接进入第二阶段SBIR提案中，我们将在现有的临床规模MPI原型中添加MFH， 具有集成温度传感的本地化MPI/MFH，并在动物尸体中验证性能 具体目标如下： 目标1.构建临床射频加热头部线圈，用于同时进行MFH和成像，并将其集成到我们的 原型临床成像仪 目标2.将基于MPI的温度传感与加热集成，以控制MFH达到治疗计划。 目标3.在体模和动物尸体中测试整个系统，为犬的临床前试验做准备 在此直接到第二阶段的建议书结束时，我们将展示集成的MPI/MFH， 局部图像引导治疗加热的原型，适用于临床研究。在我们今后的工作中， 我们计划在JHU的一个大型动物试验中测试该系统，用于治疗自发性犬GBM。