Table-top cancer treatment with microbeams

微束放射治疗(MRT)是一种创新的、全新的放射治疗方法，它利用高强度同步辐射。准直器将辐射场细分为平面微米宽的高剂量区(峰)，由数百微米宽的低剂量区(谷)隔开，而不是用与肿瘤一致的均匀剂量治疗。峰值的剂量高达数百格雷，而山谷的剂量保持在组织耐受水平以下。MRT在肿瘤治疗中与传统放射治疗同样有效，但大量临床前证据表明，MRT显著减少了对正常组织的副作用。与传统的放射治疗不同，MRT特别针对肿瘤和正常组织微环境的差异。因此，MRT在脑、肺等对辐射敏感组织的肿瘤治疗中具有重要的应用价值。然而，对世界上少数几个大型第三代同步加速器的依赖，阻碍了临床前研究和临床应用，因此，我将建立一个紧凑型微束源，允许在医院环境中进行MRT。我在过去开发了这样一种源的想法并申请了专利，我称之为线聚焦X射线管(LFxT)。它能够为MRT提供足够的束流特性，并可能适用于其他医学应用，如相衬成像。我将使用LFxT进行聚焦生物医学的体外和体内研究，以探讨MRT的机制。我将利用免疫功能正常的小鼠的同基因肿瘤模型来确定MRT诱导的毒性并测量免疫反应。此外，我将量化血管系统的形态变化，并分析MRT治疗后的旁观者信号。在我的项目结束时，前景看好的MRT方法将准备好在传统医院进行第一次临床试验。

Microbeam Radiation Therapy (MRT) is an innovative, radically new approach to radiation therapy that utilizes high intensity synchrotron radiation. Instead of treating the tumour with homogeneous tumour conform doses, a collimator subdivides the radiation field into planar micrometre wide high dose areas (peaks) separated by a few hundred micrometre wide low dose regions (valleys). Doses in the peaks reach up to several hundred Grays, while doses in the valleys stay below the tissue tolerance level. MRT is equally effective in tumour treatment as conventional radiation therapy, but drastically reduces side effects to normal tissue as shown by a significant body of pre-clinical evidence. Unlike conventional radiation therapy, MRT specifically targets differences in the tumour and normal tissue microenvironment. Therefore, MRT would be extremely valuable for the treatment of tumours in radiation sensitive tissues, such as brain and lung. However, the dependence on a few large third generation synchrotrons in the world, has impeded preclinical research and a clinical application until know.Therefore, I am going to build a compact microbeam source that allows MRT in a hospital environment. I developed and patented the idea of such a source in the past that I call Line Focus x-ray Tube (LFxT). It is able to provide adequate beam properties for MRT and may be suitable for other medical applications, such as phase contrast imaging.I will use the LFxT for focussed bio-medical in-vitro and in-vivo research in order to investigate the mechanisms underlying MRT. I am going to determine MRT induced toxicities and measure immune responses using syngeneic tumour models in immunocompetent mice. Moreover, I will quantify morphological changes in the vasculature and analyse bystander signalling after MRT treatment. At the end of my project, the promising approach of MRT will be ready for first clinical trials at conventional hospitals.