Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States of America.
True North Biopharm, LLC, Rockville, MD, United States of America.
Phys Med Biol. 2024 Jul 3;69(14). doi: 10.1088/1361-6560/ad589f.
. To fabricate and validate a novel focused collimator designed to spare normal tissue in a murine hemithoracic irradiation model using 250 MeV protons delivered at ultra-high dose rates (UHDRs) for preclinical FLASH radiation therapy (FLASH-RT) studies.. A brass collimator was developed to shape 250 MeV UHDR protons from our Varian ProBeam. Six 13 mm apertures, of equivalent size to kV x-ray fields historically used to perform hemithorax irradiations, were precisely machined to match beam divergence, allowing concurrent hemithoracic irradiation of six mice while sparing the contralateral lung and abdominal organs. The collimated field profiles were characterized by film dosimetry, and a radiation survey of neutron activation was performed to ensure the safety of staff positioning animals.. The brass collimator produced 1.2 mm penumbrae radiation fields comparable to kV x-rays used in preclinical studies. The penumbrae in the six apertures are similar, with full-width half-maxima of 13.3 mm and 13.5 mm for the central and peripheral apertures, respectively. The collimator delivered a similar dose at an average rate of 52 Gy sfor all apertures. While neutron activation produces a high (0.2 mSv h) initial ambient equivalent dose rate, a parallel work-flow in which imaging and setup are performed without the collimator ensures safety to staff.. Scanned protons have the greatest potential for future translation of FLASH-RT in clinical treatments due to their ability to treat deep-seated tumors with high conformality. However, the Gaussian distribution of dose in proton spots produces wider lateral penumbrae compared to other modalities. This presents a challenge in small animal pre-clinical studies, where millimeter-scale penumbrae are required to precisely target the intended volume. Offering high-throughput irradiation of mice with sharp penumbrae, our novel collimator-based platform serves as an important benchmark for enabling large-scale, cost-effective radiobiological studies of the FLASH effect in murine models.
. 为了在使用超高峰值剂量率 (UHDR) 的 250 MeV 质子进行临床前 FLASH 辐射治疗 (FLASH-RT) 研究的鼠半胸部照射模型中，制造和验证一种专门用于保护正常组织的新型聚焦准直器，我们设计了一种新型聚焦准直器，该准直器由我们的瓦里安 ProBeam 设计，用于成形 250 MeV UHDR 质子。六个 13 毫米孔径与历史上用于进行半胸部照射的千伏 X 射线场等效大小，经过精确加工以匹配光束发散度，允许同时对六只小鼠进行半胸部照射，同时保护对侧肺和腹部器官。准直器的场分布特性通过胶片剂量测定进行了表征，并进行了辐射调查以测量中子激活，以确保工作人员定位动物的安全性。. 该黄铜准直器产生的 1.2 毫米半影辐射场与临床前研究中使用的千伏 X 射线相当。六个孔径中的半影相似，中央孔径和外围孔径的全宽半最大值分别为 13.3 毫米和 13.5 毫米。准直器以平均 52 Gy s的速率为所有孔径提供相似的剂量。虽然中子激活会产生较高的初始环境等效剂量率（0.2 mSv h），但通过平行工作流程，在没有准直器的情况下进行成像和设置，可以确保工作人员的安全。. 由于其治疗深部肿瘤的高适形性，扫描质子在未来将更有潜力将 FLASH-RT 转化为临床治疗。然而，与其他模式相比，质子点的剂量呈高斯分布，会产生更宽的侧向半影。这在需要毫米级半影来精确靶向预期体积的小型动物临床前研究中是一个挑战。我们的新型基于准直器的平台提供了具有锐利半影的小鼠高通量照射，为在小鼠模型中进行大规模、具有成本效益的 FLASH 效应放射生物学研究提供了重要基准。
