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.

摘要/摘要 在这个SBIR赠款提案中：“结合磁性的原型临床治疗平台的开发 用于治疗脑肿瘤的颗粒成像（MPI）和磁性流体高温（MFH）”我们将发展 人类大脑大小的局部MFH/MPI系统。我们将开发成像引导的MFH处理 能够在治疗过程中闭环局部加热和断层扫描温度监测的设备。 MFH依赖于将磁性纳米颗粒递送到肿瘤，然后应用替代磁性 田地，导致组织局部加热和杀死肿瘤细胞。细胞死亡是由于热量或由 增强无线电/化学疗法的细胞毒性作用。 MFH为众多 生物医学应用，尤其是作为临床治疗的放射治疗的辅助 胶质母细胞瘤。但是，MFH目前受到近四十年临床的限制 欧洲的经验和监管批准。输送后，肿瘤内的纳米颗粒分布 可能是异构和不可预测的，导致MNP浓度低的地区不足，并且 正常组织附近的加热过多。这些问题的准确监控能力有限，使这些问题更加复杂 3D和实时的组织温度。 在此SBIR中开发的技术是通过开发第一个人类的MFH范式转变 大小的局部MFH系统。局部MFH是一种使用强磁场梯度的新技术 将MNP加热到一个小区域。该区域内的颗粒可以产生热量，而在 区域不能。我们的技术将从当前针对性的艺术状态过渡临床MFH， 区域加热到目标时机的MM精确局部加热。我们相信从区域到 精确的靶向靶向与早期靶向辐射疗法的过渡至今， 3D靶向强度调节的放射治疗。 在此直接向II阶段SBIR提案中，我们将在现有的临床规模MPI原型中添加MFH以启用 具有集成温度感测的局部MPI/MFH，并验证动物尸体的性能 通过以下特定目的： 目标1。构建一个同时MFH和成像的临床RF加热头线圈并将其集成到我们的 原型临床成像仪 AIM 2。将基于MPI的温度传感与加热相结合，以将MFH控制到治疗计划。 AIM 3。幻象和动物尸体的总体测试系统，准备狗的临床前试验 在直接到II阶段提案的结尾，我们将证明整合的MPI/MFH的精确 适用于临床研究的原型中的局部图像引导的热加热。在我们未来的工作中 我们计划在JHU的一项大型动物试验中测试该系统，以治疗赞助犬GBM。