Ahmed Mabroor, Bicher Sandra, Combs Stephanie Elisabeth, Lindner Rainer, Raulefs Susanne, Schmid Thomas E, Spasova Suzana, Stolz Jessica, Wilkens Jan Jakob, Winter Johanna, Bartzsch Stefan
Department of Radiation Oncology, School of Medicine and Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Institute of Radiation Medicine, 85764 Neuherberg, Germany.
Cancers (Basel). 2024 Jan 30;16(3):0. doi: 10.3390/cancers16030581.
Microbeam radiation therapy (MRT) is a still pre-clinical form of spatially fractionated radiotherapy, which uses an array of micrometer-wide, planar beams of X-ray radiation. The dose modulation in MRT has proven effective in the treatment of tumors while being well tolerated by normal tissue. Research on understanding the underlying biological mechanisms mostly requires large third-generation synchrotrons. In this study, we aimed to develop a preclinical treatment environment that would allow MRT independent of synchrotrons. We built a compact microbeam setup for pre-clinical experiments within a small animal irradiator and present in vivo MRT application, including treatment planning, dosimetry, and animal positioning. The brain of an immobilized mouse was treated with MRT, excised, and immunohistochemically stained against γH2AX for DNA double-strand breaks. We developed a comprehensive treatment planning system by adjusting an existing dose calculation algorithm to our setup and attaching it to the open-source software 3D-Slicer. Predicted doses in treatment planning agreed within 10% with film dosimetry readings. We demonstrated the feasibility of MRT exposures in vivo at a compact source and showed that the microbeam pattern is observable in histological sections of a mouse brain. The platform developed in this study will be used for pre-clinical research of MRT.
微束放射疗法（MRT）是一种仍处于临床前阶段的空间分割放射疗法，它使用一系列微米宽的平面X射线束。事实证明，MRT中的剂量调制在治疗肿瘤方面有效，同时正常组织对其耐受性良好。对其潜在生物学机制的研究大多需要大型第三代同步加速器。在本研究中，我们旨在开发一种独立于同步加速器的临床前治疗环境。我们在小型动物辐照器内构建了一个用于临床前实验的紧凑型微束装置，并展示了体内MRT应用，包括治疗计划、剂量测定和动物定位。对一只固定小鼠的大脑进行MRT治疗，切除后进行免疫组织化学染色，以检测γH2AX的DNA双链断裂情况。我们通过将现有的剂量计算算法调整到我们的装置并将其附加到开源软件3D-Slicer上，开发了一个全面的治疗计划系统。治疗计划中的预测剂量与薄膜剂量测定读数的误差在10%以内。我们证明了在紧凑型源处进行体内MRT照射的可行性，并表明在小鼠大脑的组织学切片中可以观察到微束图案。本研究中开发的平台将用于MRT的临床前研究。
