Carbon Nanotube-based Microbeam Radiation Therapy for Human Brain Cancer

基于碳纳米管的微束放射治疗人脑癌

• 批准号: 7982955
• 负责人: OTTO Z ZHOU
• 金额: $ 20.6万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7982955
• 关键词: Address; Animal Experimentation; Animal Model; Animals; Anodes; Area; Arts; Brain; Brain Neoplasms; CCNE1 gene; Carbon; Cathodes; Clinical; Collimator; Custom; Development; Devices; Dose; Dose-Limiting; Dose-Rate; Electron Beam; Filtration; Flowers; Glioblastoma; Glioma; Goals; Grant; Head; Heating; Histocompatibility Testing; Human; Image; Instruction; Investigation; Left; Malignant Neoplasms; Malignant neoplasm of brain; Medical Imaging; Modeling; Mus; Nanotechnology; Necrosis; Neuraxis; Normal tissue morphology; Optics; Patients; Radiation; Radiation therapy; Side; Simulate; Source; Spatial Distribution; Synchrotrons; System; Technology; Testing; Translating; Validation; base; brain tissue; clinical application; design; dosimetry; irradiation; simulation; technology development; therapy design; treatment planning; tumor; tumor eradication

PROJECT SUMMARY (See instructions): Project 4: Carbon Nanotube-based Microbeam Radiation Tfierapy 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 fissues. 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 underiying 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 huamn 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 attracfive approach for medical imaging and radiotherapy applications. In this second CCNE project we will use the CNT field emission teechnology to design the first nonsynchrotron-faclllty-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.

项目摘要（参见说明）： 项目4：基于碳纳米管的微束放射疗法治疗人脑癌 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，并将有前途的实验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癌症患者提供了极好的益处。然而，对于患有抗放射肿瘤（例如脑癌）的患者来说，这些益处大大减弱。对于这些患者来说，根除肿瘤所需的辐射毒性很大，会对正常组织造成难以忍受的损害。最终的放射治疗方法应该具有高组织类型选择性——它从本质上根除肿瘤，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，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）造成功能损伤。尽管MRT具有巨大的潜力，但尚未用于人类。 将 MRT 从实验室转移到临床存在两个主要瓶颈：1）缺乏 对潜在机制的全面了解；2）缺乏可用的 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，目前尚不存在人类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，用于治疗人类脑肿瘤，特别是胶质母细胞瘤（GBM）。目前的放射治疗对GBM的控制不佳与剂量限制正常脑组织损伤（例如脑坏死）有关。我们假设 MRT 可以有效根除包括 GBM 在内的人脑肿瘤，而不会对正常脑功能造成严重损害。因此，我们建议开发一种紧凑的 MRT 系统来治疗人类脑癌。关键的技术挑战是在微束空间分布上实现标志性的高剂量率。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 项目期间，该技术发展成为一种在技术和商业上都具有吸引力的医学成像和放射治疗应用方法。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。我们将验证基于碳纳米管的 MRT 辐射对小动物产生与基于同步加速器的 MRT 系统类似的放射生物学效应。我们将设计、模拟和验证紧凑型人体捷运系统的主要组件。我们的目标是让完整的人体 MRT 系统设计为设备制造做好准备。