The foundations of specific radiobiological effects generated by laser-accelerated protons

激光加速质子产生的特定放射生物学效应的基础

• 批准号: 401832363
• 负责人: Professor Dr. Friedrich Boege
• 金额: --
• 依托单位: Institut für Laser- und Plasmaphysik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/401832363?language=en
• 关键词: foundations; specific; radiobiological; effects; generated

Current, mainstream Radiation Therapy (RT) predominantly utilizes X-rays that show unfavorable energy deposition patterns for deep-seated tumors. Energetic-charged-particle forms of IR offer major improvements in the energy deposition patterns in a tumor. Yet, the spreading of particle therapy is currently impeded by the high cost and resource footprint. Despite such limitations particle RT is emphatically pursued worldwide and Germany co-leads this development with several advanced proton and heavy ion therapy centers. In parallel, novel charged-particle acceleration technologies evolve promising particle generators at lower cost and smaller footprint, thus promising wide distribution and feasibility for clinical trials. The present application is designed to study the radiobiological effects of one such charged-particle acceleration technology: Laser-driven, plasma-acceleration, based on laser wake-field acceleration principles. The University of Düsseldorf has made large investments in this field and Professor O. Willi operates a 200 TW laser system dedicated to the production of laser-accelerated protons (LAP) that is the basis of the proposed research. The West German Proton Center Essen (WPE) at the University Clinics Essen under Prof. B. Timmermann provides the required reference proton beams (CAP). The radiobiology of LAP is at its infancy and relevant information is only now beginning to emerge. Our consortium under the leadership of Prof. G. Iliakis at the University Clinics Essen, has cooperated for several years to study the radiobiological effects of LAP and has made seminal discoveries underpinning the proposed studies. The proposal tests the hypothesis that LAP exhibit different radiobiology because each pulse is delivered in picosecond wave-trains and consists of a large, dense ion cluster with very short inter-particle distances. As a result dose rates in the order of 109 Gy/sec are reached that are up to 9-11 orders of magnitude greater than those achieved by a cyclotron. It follows that although LAP and CAP are similarly causing water radiolysis and generate short-lived primary radicals, their biochemical and biological consequences differ as indicated by our discovery of lower production of 3-nitrotyrosine through interaction with NO-dependent pathways. Prof. C. Suschek at the University of Düsseldorf elucidates the mechanistic underpinnings of such differences. Changes in the balance of radical production will modify the type of DNA damage generated by direct/indirect effects, as well cellular stress responses. These aspects of LAP are investigated in depth by Prof. F. Boege and Prof. G. Iliakis focusing on forms of DNA double strand breaks generated and the cellular responses to them. The proposed work addresses central questions of the biology of LAP, prepares their future application in the clinic and helps to enhance the clear edge of Germany in the field of particle therapy internationally.

目前，主流放射治疗 (RT) 主要利用 X 射线，其对深部肿瘤显示出不利的能量沉积模式，从而显着改善了肿瘤中的能量沉积模式。尽管存在这些限制，粒子治疗目前仍受到全球范围内的大力推行，并且德国与多个先进的质子和重离子治疗中心共同领导了这一发展。带电粒子加速技术以更低的成本和更小的占地面积发展出有前途的粒子发生器，因此有望广泛分布和临床试验的可行性，本申请旨在研究一种此类带电粒子加速技术的放射生物学效应：激光驱动的等离子体。 -加速，基于激光尾场加速原理，杜塞尔多夫大学在这一领域投入了大量资金，O. Willi 教授运行着一套 200 TW 激光系统，专门用于产生激光加速质子 (LAP)。是拟议研究的基础。埃森大学诊所的西德质子中心 (WPE) 在 B. Timmermann 教授的领导下提供了所需的参考质子束 (CAP)。我们的联盟在埃森大学诊所 G. Iliakis 教授的领导下，已经合作研究 LAP 的放射生物学效应数年，并取得了开创性的发现。该提案测试了 LAP 表现出不同放射生物学的假设，因为每个脉冲都以皮秒波列形式传递，并且由一个大而密集的离子簇组成，粒子间距离非常短，因此剂量率按顺序排列。达到 109 戈瑞/秒，比回旋加速器高出 9-11 个数量级。 由此可见，虽然 LAP 和 CAP 类似地引起水辐射分解并产生短寿命的初级。杜塞尔多夫大学的 C. Suschek 教授通过与 NO 依赖性途径的相互作用发现了 3-硝基酪氨酸的产量降低，这表明它们的生化和生物学后果有所不同，这阐明了这种平衡变化的机制基础。 F. Boege 教授和 G. G. 教授深入研究了 LAP 的这些方面。 Iliakis 专注于 DNA 双链断裂的形式以及细胞对它们的反应，解决了 LAP 生物学的核心问题，为它们未来在临床中的应用做好了准备，并有助于增强德国在粒子领域的明显优势。国际治疗。