Radiobiology Investigations of Ions Heavier than Protons

比质子重的离子的放射生物学研究

• 批准号: 8623538
• 负责人: Kathryn Dale Held
• 金额: $ 18.05万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8623538
• 关键词: Address; Apoptosis; Argon; Autophagocytosis; Biological; Biology; Body Surface; Boron; Carbon; Carbon ion; Cell Cycle; Cell Cycle Arrest; Cell Death; Cell Line; Cells; Characteristics; Charge; Clinical; Clinical Research; DNA Repair; Data; Deposition; Development; Distal; Distant; Dose; Dose Fractionation; Educational workshop; Effectiveness; Fibroblasts; Funding Mechanisms; Future; Germany; Goals; Gold; Grant; Heavy Ions; Helium; Human; Induction of Apoptosis; Investigation; Ions; Italy; Japan; Knowledge; Laboratories; Linear Energy Transfer; Lithium; Location; Malignant Neoplasms; Maps; Mitotic; Modeling; Nature; Neon; Normal Cell; Normal tissue morphology; Oxygen; Patients; Penetration; Photons; Physics; Protons; Radiation; Radiation Tolerance; Radiation therapy; Radiobiology; Recovery; Research; Resistance; Rest; Surface; Tail; Testing; Therapeutic Studies; Time; Tissues; United States National Aeronautics and Space Administration; Variant; Work; biophysical model; cancer therapy; cell killing; cell type; clinically relevant; design; insight; interest; irradiation; neoplastic cell; novel; particle; particle beam; public health relevance; research and development; response; systematic biology; tumor

DESCRIPTION (provided by applicant): Charged particle beams, such as protons, are advantageous for cancer therapy because the finite range of the particles results in relatively little dose at the surface of a patient's body while depositing greater dose just before the particles come to rest in tissue (the Bragg peak). Because of this dose distribution advantage, the use of protons in cancer treatment has expanded greatly in recent years. In addition to the physical dose distribution, ions heavier than protons have increased biological advantages because of greater cell killing, decreased oxygen effect and smaller variation in radiation sensitivity through the cell cycle in replicating cells. Many of these biological advantages were demonstrated originally in the US and the early clinical studies of heavy ions were in the US. This knowledge led to development of five carbon ion therapy centers overseas, but there are none in the US. Importantly, many critical biology and physics questions remain about particles for therapy use, and this paucity of data is a significant impediment to exploiting the full potental of charged particle therapy. In anticipation that, in the not-too-distant future, therapy with ions heavier than protons will be resurrected in the US, fundamental radiation biology studies are proposed herein that will provide new data needed to guide R&D for such a facility. The proposed studies will utilize the unique facilities at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), currently the only location in the US where biological studies with ions heavier than protons can be conducted, to perform specific, highly clinically-relevant, cutting-edge studies. The overall goal is to address whether carbon is the optimal ion species for cancer therapy with particles and what tumor characteristics should be used to identify the tumors that would benefit most from ion therapy. The specific aims are to: (1) determine biological effectiveness of several ion species (atomic numbers from helium to oxygen) of clinical interest compared to 200 MeV protons as a function of depth in tissue equivalent material for selected tumor and normal cell types of varying radiation responsiveness and (2) assess the mode of cell death (apoptosis, permanent cell cycle arrest, mitotic catastrophe, autophagy) in cells irradiated with heavier ions compared to protons. We will test the hypothesis that the greater effectiveness of heavy ion-induced cell killing for cell types that show greater cell recovery after low LET radiations (i.e., low ¿/¿ ratios) results from increased induction of apoptosis in cells that are normally resistant to low LET-radiation-induced apoptosis. This systematic study will provide novel information on which ion species might be most useful for therapy, increase insight into which specific tumor types might be best treated with specific ions, and provide quantitative data to facilitate novel biophysical modeling of ion beams for therapy. This information will help guide planning for a heavier-than-protons facility in the US.

描述(申请人提供)：带电粒子束，如质子，对癌症治疗是有利的，因为粒子的有限范围导致患者身体表面的剂量相对较小，而在粒子进入组织(布拉格峰)之前沉积更大的剂量。由于这种剂量分布优势，质子在癌症治疗中的使用近年来得到了极大的扩展。除了物理剂量分布外，重于质子的离子在复制细胞中具有更大的细胞杀伤力、更低的氧气效应和更小的辐射敏感性变化，从而增加了生物优势。其中许多生物学优势最初是在美国展示的，重离子的早期临床研究是在美国进行的。这一知识导致了海外五个碳离子治疗中心的发展，但美国一个也没有。重要的是，许多关于用于治疗的粒子的关键生物学和物理学问题仍然存在，这种数据的匮乏是充分发挥带电粒子治疗潜力的重大障碍。预计在不太遥远的将来，离子疗法 重于质子的辐射生物学研究将在美国复活，这里提出的基本辐射生物学研究将提供指导此类设施研发所需的新数据。拟议的研究将利用布鲁克海文国家实验室(BNL)的NASA空间辐射实验室(NSRL)的独特设施进行特定的、与临床高度相关的尖端研究，该实验室目前是美国唯一可以进行比质子重的离子的生物研究的地点。总体目标是解决碳是否是粒子癌症治疗的最佳离子物种，以及应该使用什么肿瘤特征来识别从离子治疗中受益最大的肿瘤。具体目的是：(1)确定几种临床上有意义的离子物种(从氦到氧的原子序数)与200 MeV质子的生物有效性，作为选定肿瘤和不同辐射响应性的正常细胞类型的组织等效材料深度的函数，以及(2)评估与质子相比，较重离子照射的细胞的死亡模式(细胞凋亡、永久性细胞周期停滞、有丝分裂灾难、自噬)。我们将检验这一假设，即重离子诱导的细胞杀伤对不同类型的细胞更有效 在低LET辐射(即低/低比率)后，显示出更大的细胞恢复，这是由于在正常情况下对低LET辐射诱导的细胞凋亡具有抵抗力的细胞的凋亡诱导增加所致。这项系统的研究将提供关于哪些离子物种可能对治疗最有用的新信息，增加对哪些特定类型的肿瘤可能最好地使用特定离子的洞察，并提供量化数据以促进用于治疗的离子束的新的生物物理模型。这些信息将有助于指导规划一个比质子更重的设施 美国。