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

摘要/摘要 在这份SBIR赠款提案中，“开发一种结合磁力的临床治疗平台原型” 粒子成像(MPI)和磁流体热疗(MFH)治疗脑肿瘤 一个人脑大小的、集成的局部MFH/MPI系统。我们将开发一种影像引导的MFH治疗方法 可在治疗过程中进行闭环局部加热和断层温度监测的装置。 MFH依赖于将磁性纳米颗粒输送到肿瘤，然后应用交变磁化 磁场，导致组织局部加热和肿瘤细胞被杀死。细胞死亡是由于高温或由 增强放化疗的细胞毒作用。MFH提供了相当大的潜力 生物医学的应用，尤指作为放射治疗的辅助手段，用于临床治疗复发性肿瘤 胶质母细胞瘤。然而，在经过近40年的临床治疗后，MFH目前仍存在局限性 在欧洲的经验和监管批准。在交付后，纳米颗粒在肿瘤内的分布 可能是异质性和不可预测的，导致在MNP浓度较低的地区待遇不足，以及 正常组织附近过热。这些问题因准确监控的能力有限而变得更加复杂 三维和实时的组织温度。 这项在SBIR中开发的技术通过开发第一个人类-- 本地化MFH系统的规模。局部化MFH是一种利用强磁场梯度 将MNP供暖限制在很小的区域内。该区域内的粒子可以产生热量，而那些位于该区域之外的粒子 区域不能。我们的技术将使临床上的MFH从目前的松散靶向， 区域加热至毫米-目标组织的精确定位加热。我们认为，从地区到 精确靶向可与早期、松散靶向的放射治疗过渡到今天相媲美， 3D靶向调强放射治疗。 在这个直接到第二阶段的SBIR计划中，我们将在我们现有的临床规模MPI原型中添加MFH，以实现 集成温度传感的定位MPI/MFH，并在动物身体上验证其性能 通过以下具体目标： 目的1.建立一个临床射频热头线圈，用于同时进行MFH和成像，并将其集成到我们的 临床成像仪样机 目的2.将基于MPI的温度传感与加热相结合，将MFH控制到治疗计划中。 目的3.在幻影和动物身体上测试整个系统，为狗的临床前试验做准备 在此直接到第二阶段计划的末尾，我们将展示集成的MPI/MFH 适用于临床研究的原型机中的局部图像引导治疗加热。在我们今后的工作中， 我们计划在JHU的一项大型动物试验中测试这一系统，以治疗自发性犬的GBM。

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.