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: 8540379
• 负责人: OTTO Z ZHOU
• 金额: $ 17.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8540379
• 关键词: Address; Animal Experimentation; Animal Model; Animals; Anodes; Area; Brain; Brain Neoplasms; CCNE1 gene; Cancer Center; Carbon Nanotubes; 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 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.

项目摘要（请参阅说明）： 项目4：基于碳纳米管的人脑癌的微束放射治疗 我们将开发具有纳米技术的紧凑型微束放射疗法（MRT）系统，并将有希望的实验放疗从动物研究转化为广泛的临床应用。 如今，最先进的放射治疗为许多放射敏感性癌症患者提供了极大的好处。但是，对于辐射耐药性肿瘤（例如脑癌）的患者，这些益处大大减少。对于这些患者而言，消除肿瘤所需的疗效是如此有毒，以至于可能对正常组织造成无法忍受的损害。最终的放射疗法应具有高组织类型的选择性 - 它本质地消除了肿瘤，同时使正常的组织功能完好无损。 MRT可能只是这种放射疗法的方法。令人信服的动物研究表明，超高剂量（100s Gy）的单一MRT治疗消除了肿瘤，而没有对正常组织的功能损害，包括发育中的中枢神经系统的组织。尽管它的潜力巨大，但尚未用于人类。 将MRT从板凳侧转换为床边有两个主要的瓶颈：1）缺乏对潜在机制的全面理解，以及2）缺乏可访问的MRT辐射装置。世界上只有基于同步加速器的动物研究捷运系统，当今没有人类MRT系统。我们的目标是开发一种基于纳米技术的人类脑肿瘤，尤其是胶质母细胞瘤（GBM）的紧凑型人类MRT系统，通过当前疗效治疗对GBM的控制不佳与剂量限制了限制正常脑组织损伤（如脑坏死）。我们假设MRT可以有效地消除包括GBM在内的人类肿瘤，而没有严重的正常脑功能损害。因此，我们建议开发一种针对人脑癌的紧凑型MRT系统。关键的技术挑战是在微束空间分布下实现标志性高剂量率。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的多光束田间发射X射线技术。在第一个CCNE项目中，该技术蓬勃发展为一种技术和商业上有吸引力的医学成像和放射疗法应用方法。在第二个CCNE项目中，我们将使用CNT场排放技术来设计第一个针对人脑癌的基于非氯替型的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作用。我们将设计，模拟和验证紧凑型人类MRT系统的主要组成部分。我们的目标是准备完整的人类MRT系统设计，以便进行设备制造。