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，利用高强度同步辐射。准直器不是用均匀的肿瘤适形剂量治疗肿瘤，而是将辐射场细分为由几百微米宽的低剂量区域（谷）分开的平面微米宽的高剂量区域（峰）。峰值中的剂量高达几百格雷，而谷值中的剂量保持在组织耐受水平以下。MRT在肿瘤治疗中与常规放射治疗同样有效，但显著减少了对正常组织的副作用，如大量临床前证据所示。与传统的放射治疗不同，MRT专门针对肿瘤和正常组织微环境的差异。因此，MRT对于治疗放射敏感组织（如脑和肺）中的肿瘤将是非常有价值的。然而，对世界上少数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，直到知道。因此，我打算建立一个紧凑的微束源，使MRT在医院环境中。我在过去开发了这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提供足够的光束特性，并可能适用于其他医学应用，如相位对比Imaging.I将使用LFxT聚焦生物医学体外和体内研究，以调查MRT的机制。我将确定MRT诱导的毒性，并使用免疫活性小鼠的同基因肿瘤模型测量免疫反应。此外，我将量化血管的形态学变化，并分析MRT治疗后的旁观者信号。在我的项目结束时，有前途的MRT方法将在传统医院进行首次临床试验。

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.