Radiobiology Investigations of Ions Heavier than Protons

比质子重的离子的放射生物学研究

基本信息

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
项目类别：
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

项目摘要

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（由适用提供）：带电的颗粒梁（例如质子）对癌症治疗是有利的，因为颗粒的有限范围会导致患者身体表面的剂量相对较少，而在颗粒静止在组织（Bragg Peak）之前，则沉积更大的剂量。由于具有这种剂量分布优势，近年来，质子在癌症治疗中的使用大大扩展。除了物理剂量分布外，由于细胞杀伤的较大，氧气效应降低，辐射敏感性降低，通过复制细胞中细胞周期的辐射敏感性较小，因此比质子重的离子具有增加的生物学优势。这些生物学优势中有许多最初在美国证明了重新离子的早期临床研究。这些知识导致了五个碳离子疗法中心的发展，但在美国没有。重要的是，许多关键的生物学和物理学问题仍然存在于用于治疗的颗粒上，而数据很少是利用带电颗粒疗法的全部潜力的重要障碍。在预期的是，在不太遥远的未来，对离子的治疗在美国将恢复比质子重的重，本文提出了基本的辐射生物学研究，该研究将提供新的数据，以指导这种设施的研发。拟议的研究将利用Brookhaven国家实验室（BNL）的NASA太空辐射实验室（NSRL）的独特设施，目前，美国唯一可以进行比质子更重的生物学研究的地方，可以进行比质子重的生物学研究，以进行特定的特定临床，临床上较高的尖端，尖端的尖端研究。总体目标是解决碳是否是用于颗粒癌症治疗的最佳离子物种，以及应使用哪种肿瘤特征来识别将受益于离子疗法最大的肿瘤。 The specific aims are to: (1) determined 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 heatier离子与质子相比。我们将检验以下假设，即重离子引起的细胞杀死的较高有效性对于细胞类型在低辐射（即低€/€比率）后，显示出更大的细胞恢复是由于通常抗低辐射诱导诱导的细胞凋亡的细胞中凋亡的诱导增加而导致的。这项系统的研究将提供有关哪些离子物种可能对治疗最有用的新信息，增加对哪些特定肿瘤类型最好使用特定离子进行治疗的见解，并提供定量数据以促进离子束治疗的新型生物物理模型。此信息将有助于指导计划的计划美国。