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 在此 SBIR 拨款提案中，“开发结合磁性技术的原型临床治疗诊断平台” 我们将开发用于治疗脑肿瘤的粒子成像（MPI）和磁流体热疗（MFH） 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。 能够在治疗过程中进行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至肿瘤，然后应用交变磁场 场，导致组织局部加热并因热量或细胞死亡而死亡。 增强放射/化疗的细胞毒性作用为许多人提供了巨大的潜力。 生物医学应用，特别是在复发性癌症的临床治疗中作为放射治疗的辅助手段 然而，经过近四十年的临床研究，胶质母细胞瘤目前仍然存在局限性。 欧洲的经验和监管批准。交付后，纳米颗粒在肿瘤内的分布。 可能是异质且不可预测的，导致 MNP 浓度低的地区治疗不足，并且 正常组织附近的过度加热使这些问题因准确监测的能力有限而变得更加复杂。 3D 实时组织温度。 本次 SBIR 中开发的技术通过开发第一个人类- 小型局部 MFH 系统 局部 MFH 是一种利用强磁场梯度来实现的新技术。 将 MNP 加热限制在一个小区域内，该区域内的粒子可以产生热量，而区域外的粒子则可以产生热量。 我们的技术将使临床 MFH 从目前松散目标的技术水平转变。 我们相信这种从区域加热到毫米级精确的目标组织局部加热的转变。 精确靶向可与早期、松散靶向放射治疗到现在的过渡相媲美， 3D 靶向调强放射治疗。 在这个直接进入 II 期 SBIR 提案中，我们将把 MFH 添加到我们现有的临床规模 MPI 原型中，以实现 具有集成温度传感功能的本地化 MPI/MFH，并在动物尸体中验证其性能 通过以下具体目标： 目标 1. 构建用于同步 MFH 和成像的临床射频加热头线圈，并将其集成到我们的 原型临床成像仪 目标 2. 将基于 MPI 的温度传感与加热相集成，以根据治疗计划控制 MFH。 目标 3. 在体模和动物尸体中测试整个系统，为狗的临床前试验做准备 在直接进入第二阶段提案结束时，我们将展示集成的 MPI/MFH，以精确地实现 在适合临床研究的原型中进行局部图像引导治疗加热。 我们计划在约翰霍普金斯大学的一项大型动物试验中测试该系统，以治疗自发性犬 GBM。