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脑肿瘤 我们将开发一种基于纳米技术的紧凑型微束放射治疗(MRT)系统，并将前景广阔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对辐射敏感的癌症患者提供了极好的益处。然而，对于患有抗辐射肿瘤(如脑癌)的患者来说，这些好处就会大大减少。对于这些患者来说，根除肿瘤所需的放射性物质毒性太大，可能会对正常组织造成无法忍受的损害。最终的放射治疗方法应该具有很高的组织类型选择性--它在本质上根除肿瘤，同时保持正常的组织功能不变。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，单次超高剂量(100s Gy)的MRT治疗可以根除肿瘤，而不会对正常组织包括发育中的中枢神经系统造成功能损害。尽管捷运具有巨大的潜力，但尚未在人类身上得到应用。 将MRT从工作台转移到床边有两个主要瓶颈：1)缺乏对潜在机制的全面了解；2)缺乏可获得的MRT照射设备。世界上只有基于同步加速器的动物研究MRT系统，而今天还没有人类MRT系统。我们的目标是开发一种基于纳米技术的紧凑型人体MRT系统，用于治疗人脑肿瘤，特别是胶质母细胞瘤(GBM)。目前放射治疗对GBM的控制不佳与脑坏死等正常脑组织损伤的剂量限制有关。我们推测，MRT可以有效地根除包括GBM在内的人脑肿瘤，而不会对正常的脑功能造成严重损害。因此，我们建议开发一种紧凑的人脑肿瘤MRT系统。关键的技术挑战是实现微束空间分布的高剂量率。我们的方法是利用我们团队首创的基于碳纳米管的空间分布式多束场发射x射线技术。在第一个CCNE项目中，该技术发展成为一种在技术和商业上具有吸引力的方法，用于医学成像和放射治疗应用。在第二个CCNE项目中，我们将使用碳纳米管场发射技术来设计第一个针对人类脑癌的基于非同步加速器设施的MRT系统。我们将验证基于CNT的MRT辐射在小动物身上产生的放射生物学效应与基于同步加速器的MRT系统相似。我们将设计、模拟和验证紧凑型人类MRT系统的主要组件。我们的目标是使完整的人类MRT系统设计为设备制造做好准备。

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.