6 MeV/amu ion linac for deep-penetration microbeam and millimeter-beam charged-particle irradiations in small animals and biological tissues

6 MeV/amu 离子直线加速器，用于小动物和生物组织的深穿透微束和毫米束带电粒子照射

• 批准号: 9493886
• 负责人: DAVID JONATHAN BRENNER
• 金额: $ 200万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9493886
• 关键词: 3-Dimensional; Affect; Animals; Biological; Biomedical Technology; Breast; Bystander Effect; Caliber; Carbon ion; Charge; Clinical; Communities; Deposition; Funding; Heavy Ions; High-LET Radiation; Immunologics; Ions; Linear Accelerator Radiotherapy Systems; Normal tissue morphology; Olives - dietary; Pancreas; Particle Accelerators; Penetration; Prostate; Prostatic Neoplasms; Protocols documentation; Protons; Radiation; Radiation therapy; Radiobiology; Radiology Specialty; Rectal Neoplasms; Recurrence; Research; Resources; Roentgen Rays; Signal Transduction; Site; Thick; Thinness; Tissue Model; Tissues; United States National Institutes of Health; Universities; base; cancer radiation therapy; high risk; in vivo Model; interest; irradiation; melanoma; millimeter; monolayer; pancreatic neoplasm; particle; response; tool; tumor

Summary: Funds are requested for a 6 MeV/amu linear accelerator (linac), which will be used to generate ion beams spanning a wide range of radiation qualities having penetrations of up to 1 mm in tissue. These beams will then be focused into microbeams (beam diameter of a few microns) or millimeter-sized beams, allowing systematic mechanistic studies of tumor responses and normal-tissue responses relating to contemporary heavy-ion beam radiotherapy. The studies that will be facilitated by the linac are mechanistically- motivated and do not focus explicitly on specific protocols for heavy-ion cancer radiotherapy. The linac will be located at the Radiological Research Accelerator Facility (RARAF) at Columbia University which is an NIH- funded National Biomedical Technology Resource Center dedicated to understanding the radiobiological mechanisms by which different types of radiation affect living matter. There has been increasing recent interest from the radiation therapy and the radiation biology communities in heavy charged-particle radiotherapy, particularly carbon ions, to treat hard-to-treat high-risk tumors, particularly those that have already spread beyond the primary site. These particles deposit energy in a more spatially-dense way (“high LET”) than do X rays or protons. Examples of tumors that have been shown clinically to benefit from high-LET radiation therapy are locally advanced pancreatic tumors, late-stage prostate tumors, and locally recurrent rectal tumors. Based on their efficacy in treating tumors that have spread beyond the primary site, it is reasonable to assume that that the high-LET radiations are eliciting a long-range response, through bystander, abscopal or immunological mechanisms, of a type that may not be induced by conventional radiotherapy. In summary, there is a great deal of interest in the radiotherapy / radiobiology community in trying to understand the mechanisms underlying this heavy-ion high-LET induced long-range signal transduction, particularly in the context of hard-to treat tumors. This is reflected in the range of projects in this application, that include high-LET mechanistic studies for pancreas (Olive), melanoma (Guha), prostate (Shen), breast (Demaria), as well as normal tissue sparing (Fornace), and bystander-effect range estimation (Brenner). Microbeams and millimeter-sized beams, which are produced at RARAF, allow the energy deposition to be highly localized, and so represent an ideal tool to study long-range damage signaling mechanisms. Using the current 2.5 MeV/amu accelerator at RARAF, the spatial range of the particles that can be produced is sufficient only to irradiate cellular monolayers or extremely thin tissues. However the long-range damage signal transduction endpoints of contemporary interest here need to be studied with in-vivo models and 3-D tissue models, which are too thick to be penetrated by 2.5 MeV/amu ions. Thus the spatial penetration of the charged particles needs to be increased, by increasing the energy the particle accelerator. To meet the needs of the users, the available range of the high-LET charged particles needs to be increased by factors of 3 to 4 - requiring ion energies at RARAF of 6 MeV/amu.

摘要：要求资金用于6 MeV/AMU线性加速器（LINAC），该加速器将用于生成 离子光束横向横向辐射质量，其渗透在组织中的穿透性高达1毫米。这些 然后，梁将聚焦于微梁（几微米的光束直径）或毫米大小的梁， 允许对肿瘤反应的系统机械研究和与正常组织的反应有关 当代重型离子光束放射疗法。 Linac将准备的研究是机械机械的 动机，不明确地专注于重型离子癌放射疗法的特定方案。利纳克将是 位于哥伦比亚大学的放射学研究加速器设施（RARAF），这是NIH- 资助的国家生物医学技术资源中心致力于理解放射生物学 不同类型的辐射影响生活物质的机制。最近的兴趣增加了 从重型电荷放射疗法中的放射疗法和辐射生物学群落中 特别是碳离子，以治疗难以治疗的高风险肿瘤，尤其是那些已经扩散的肿瘤 超越主要站点。这些颗粒以更空间密集的方式（“高let”）与x相比 射线或质子。在临床上显示的肿瘤的例子是从高质LET放射治疗中受益的例子 是局部晚期胰腺肿瘤，晚期前列腺肿瘤和局部复发的直肠肿瘤。基于 关于它们在治疗主要部位以外传播的肿瘤的效率上，可以合理地假设 通过旁观者，脱离或免疫学 机制，一种可能不受常规放射疗法诱导的类型。总而言之 放射疗法 /放射生物学社区的兴趣交易试图了解基本机制 这种重型离子高LET引起的远程信号转导，尤其是在难以治疗的背景下 肿瘤。这反映在本应用程序中的项目范围内，其中包括高LET机械研究 对于胰腺（橄榄），黑色素瘤（瓜），前列腺（沉），乳房（demaria）以及正常的组织保留 （Fornace）和旁观者效应范围估计（Brenner）。微束和毫米大小的光束，它们 是在Raraf生产的，允许能源矿床高度局部，因此代表了理想的工具 研究远程损坏信号传导机制。使用当前的2.5 MEV/AMU在Raraf， 可以生产的颗粒的空间范围足以照射细胞单层或 非常薄的组织。但是，现代兴趣的远程损坏信号转导终点 这里需要使用体内模型和3-D组织模型进行研究，这些模型太厚而无法穿透2.5 Mev/Amu离子。通过增加，需要增加带电颗粒的空间渗透 能量粒子加速器。为了满足用户的需求，可用的高额电荷范围 需要通过3至4的因子增加颗粒，在6 MeV/AMU的RARAF时需要离子能量。