Carbon Nanotube-based Microbeam Radiation Therapy for Human Brain Cancer

项目总结（见说明）： 项目4：基于碳纳米管的微束放射治疗人类脑癌 我们将开发一种纳米技术支持的紧凑型微束放射治疗（MRT）系统，并将有前途的实验性放射治疗从动物研究转化为广泛的临床应用。 当今最先进的放射治疗为许多放射敏感性癌症患者提供了极好的益处。然而，这些益处对于患有放射抗性肿瘤（如脑癌）的患者会大大减少。对于这些病人来说，根除肿瘤所需的放射线毒性很大，可能对正常组织造成无法忍受的损伤。最终的放射治疗方法应该具有高组织类型选择性-它本质上根除肿瘤，同时保持正常组织功能完整。MRT可能就是这样一种放射治疗方法。令人信服的动物研究表明，一个单一的MRT治疗的100倍剂量（100戈瑞戈伊）根除肿瘤没有功能损害正常组织，包括发展中的中枢神经系统。尽管MRT具有巨大的潜力，但它尚未用于人类。 在将MRT从台侧转换到床边时存在两个主要瓶颈：1）缺乏对潜在机制的全面理解，以及2）缺乏可访问的MRT辐照设备。世界上只有基于同步加速器的动物研究MRT系统，目前还没有人类MRT系统。我们的目标是开发一种基于纳米技术的紧凑型人类MRT系统，用于人类脑肿瘤，特别是胶质母细胞瘤（GBM）。目前的放射治疗对GBM的不良控制与剂量限制正常脑组织损伤如脑坏死有关。我们假设MRT可以有效地根除包括GBM在内的人类脑肿瘤，而不会严重损害正常脑功能。因此，我们建议开发一个紧凑的MRT系统，用于人类脑癌。关键的技术挑战是在微束空间分布上实现高剂量率的签名。我们的方法是利用我们团队开创的基于碳纳米管的空间分布多束场发射X射线技术。在第一个CCNE项目期间，该技术发展成为医学成像和放射治疗应用的技术和商业上有吸引力的方法。在第二个CCNE项目中，我们将使用CNT场发射技术设计第一个针对人类脑癌的非同步加速器MRT系统。我们将验证基于CNT的MRT辐射对小动物产生与基于同步加速器的MRT系统相似的放射生物学效应。我们将设计，模拟和验证紧凑型人体MRT系统的主要组件。我们的目标是有完整的人体MRT系统设计准备设备制造。

PROJECT SUMMARY (See instructions): Project 4: Carbon Nanotube-based Microbeam Radiation Therapy for Human Brain Cancer We will develop a nanotechnology-enabled compact microbeam radiation therapy (MRT) system and translate the promising experimental radiotherapy from animal research to widespread clinical application. State-of-the-art radiotherapy today provides excellent benefits for many patients with radiosensitive cancers. However, these benefits greatly diminish for patients with radioresistant tumors, such as brain cancers. For these patients the radiafion, needed to eradicate the tumor is so toxic that it can cause intolerable damage to normal tissues. An ultimate radiotherapy approach should have high tissue type selectivity - it intrinsically eradicates tumor while leaving normal tissue function intact. MRT may be just such a radiotherapy approach. Convincing animal studies show that a single MRT treatment of ultrahigh dose (100s Gy) eradicates tumor without functional damage to normal tissue including that of the developing central nervous system. Despite its enormous potential MRT has not been used on human. There are two major bottlenecks In translating MRT from bench-side to bedside: 1) the lack of comprehensive understanding of the underlying mechanism and 2) the lack of accessible MRT irradiation devices. There are only synchrotron-based animal research MRT systems In the world, and no human MRT system exists today. Our goal is to develop a nanotechnology-based compact human MRT system for human brain tumors, especially glioblastoma (GBM), The poor control of GBM by current radiafion therapy is related to the dose limiting normal brain tissue damage such as brain necrosis. We hypothesize that MRT can effectively eradicate human brain tumors including GBM without severe normal brain function damage. We therefore propose to develop a compact MRT system for human brain cancers. The key technical challenge is to achieve the signature high dose rate at the microbeam spatial distribution. Our approach is to utilize the carbon nanotube based spatially distributed multi-beam field emission x-ray technology that was pioneered by our team. During the first CCNE project the technology blossomed into a technologically and commercially attractive approach for medical imaging and radiotherapy applications. In this second CCNE project we will use the CNT field emission technology to design the first nonsynchrotron-facility-based MRT system targeted for human brain cancer. We will validate that the CNTbased MRT radiation produces similar radiobiological effects on small animals as the synchrotron based MRT system. We will design, simulate, and validate major components of the compact human MRT system. Our target is to have the complete human MRT system design ready for device fabrication.