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（由申请人提供）：带电粒子束，例如质子，对于癌症治疗是有利的，因为粒子的有限范围导致患者身体表面的剂量相对较小，而在粒子即将静止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应用近年来大大扩展。除了物理剂量分布之外，比质子重的离子还具有更多的生物学优势。在复制细胞的细胞周期中，更大的细胞杀伤力、更低的氧效应以及更小的辐射敏感性变化，其中许多生物学优势最初是在美国得到证明的，并且重离子的早期临床研究是在美国进行的。海外有五个碳离子治疗中心，但美国没有。重要的是，有关治疗使用的粒子的许多关键生物学和物理学问题仍然存在，而数据的缺乏是充分利用带电粒子治疗潜力的重大障碍。预计，在不远的将来，离子疗法比质子重的原子将在美国复兴，本文提出了基础辐射生物学研究，这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美国宇航局空间辐射实验室（NSRL）的独特设施。国家实验室 (BNL) 是目前美国唯一可以进行比质子重的离子进行生物学研究的场所，其总体目标是解决碳是否是最佳选择的问题。粒子癌症治疗的离子种类以及应使用哪些肿瘤特征来识别最能从离子治疗中受益的肿瘤具体目标是：（1）确定几种离子种类（从氦到氧的原子序数）的生物有效性。与 200 MeV 质子相比，作为不同辐射反应性的选定肿瘤和正常细胞类型的组织等效材料深度的函数，具有临床意义；(2) 评估细胞死亡模式（细胞凋亡、永久性细胞周期停滞、有丝分裂灾难、与质子相比，用重离子照射的细胞中的自噬）我们将检验以下假设：重离子诱导的细胞杀伤作用对细胞类型更有效。研究表明，低 LET 辐射（即低 ¿/¿ 比率）后细胞的恢复率更高，这是由于通常对低 LET 辐射诱导的细胞凋亡具有抵抗力的细胞中细胞凋亡的诱导增加所致。这项系统研究将为哪些离子种类可能提供新的信息。对治疗最有用，深入了解哪些特定肿瘤类型最适合用特定离子治疗，并提供定量数据以促进离子束治疗的新型生物物理模型。这些信息将有助于指导治疗规划。重于质子的设施美国。