Improving preclinical proton radiation dosimetry using a biologically relevant murine dosimetry phantom

使用生物学相关的小鼠剂量测定模型改进临床前质子辐射剂量测定

• 批准号: NC/W002256/1
• 负责人: Emma Biglin
• 金额: $ 15.5万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FW002256%2F1
• 关键词: Improving; preclinical; proton; radiation; dosimetry

The goal of radiotherapy (RT) in the treatment of cancer is to deliver as much radiation dose to the tumour, whilst minimising the amount of dose delivered to the surrounding normal tissue. Proton beam therapy (PBT) is an alternate form of RT, delivering high energy particles (protons) rather than conventional x-rays (photons) to a tumour. The favourable dose deposition of protons follows a low entrance dose culminating in a steep dose gradient and rapid fall off (Bragg peak), increasing the precision of the dose delivery to the tumour. Due to the overall cost and technology required to generate protons, experiments are often performed in dedicated research rooms within a clinical department, using equipment designed for human treatment. The significant size difference between a human and a mouse makes it difficult to utilise the Bragg peak dose distribution within the small animal so often the initial plateau region of the beam is used to irradiate the target. However, this means the beam extends beyond the target as the beam energy is too high to be attenuated by the small animal and, consequently, healthy tissue is irradiated increasing toxicity. To improve the precision of the irradiation, and scale down the beam to the small animal size, a variety of techniques and equipment across institutions are used, including range shifters, energy degraders, shielding or collimators.The aim of this study is to adapt a previously developed 3D printed mouse-shaped tool (phantom) to measure proton dose using radiochromic film to ensure accurate proton dose delivery at the small animal scale in our laboratory. We aim to validate this against measurements of DNA damage in 3D matrices of tumour cells encapsulated in a hydrogel bead. Following this, the phantom will be delivered to multiple international institutions as part of a dose measurement audit, testing the techniques used and comparing the planned and delivered doses. This will be facilitated through our existing collaborations with the Inspire project and the Particle Therapy Co-operative Group (PTCOG). Currently, a small number of animals (~200) are used in pilot studies to test the suitability of different equipment to reduce the beam size to suit specific experiments. Through the multicentre audit we aim to show direct users that the phantom we have developed can be a suitable replacement for these animals. The phantom can also be used as a mouse substitute to refine experiments and streamline the set-up, reducing the time the animals are under anaesthesia or immobilised. According to a literature search, in the last 5 years ~1300 mice were used in proton research but this number is set to rise as proton beam technology becomes more widely available. Regular use of the tool to measure the dose output and identify any problems will increase confidence in the results, therefore reducing the numbers of animal required to achieve statistically significant data and refining the dose delivery to minimise potential toxicity.

放射治疗（RT）在癌症治疗中的目标是向肿瘤输送尽可能多的辐射剂量，同时最大限度地减少输送到周围正常组织的剂量。质子束治疗（PBT）是RT的替代形式，将高能粒子（质子）而不是传统的X射线（光子）输送到肿瘤。质子的有利剂量沉积遵循低入射剂量，最终导致陡峭的剂量梯度和快速下降（布拉格峰），增加了向肿瘤的剂量递送的精度。由于产生质子所需的整体成本和技术，实验通常在临床部门内的专用研究室中进行，使用为人类治疗设计的设备。人类和小鼠之间的显著尺寸差异使得难以利用小动物内的布拉格峰值剂量分布，因此通常使用射束的初始平台区域来照射目标。然而，这意味着射束延伸超出目标，因为射束能量太高而不能被小动物衰减，因此，健康组织被照射，增加毒性。为了提高照射的精度，并将光束按比例缩小到小动物的大小，使用了各种跨机构的技术和设备，包括范围移位器，能量降能器，屏蔽或准直器。本研究的目的是适应先前开发的3D打印鼠标形状的工具（幻影）利用辐射变色胶片测量质子剂量，以确保在我们实验室的小动物规模的质子剂量输送的准确性。我们的目的是验证这对测量的DNA损伤的3D矩阵的肿瘤细胞封装在一个水凝胶珠。在此之后，体模将被交付给多个国际机构，作为剂量测量审计的一部分，测试所使用的技术并比较计划和交付的剂量。这将通过我们现有的合作，与pmire项目和粒子治疗合作组（PTCOG）。目前，少量动物（约200只）用于试点研究，以测试不同设备的适用性，以减少光束大小，以适应特定的实验。通过多中心审核，我们的目标是向直接用户展示，我们开发的幻影可以成为这些动物的合适替代品。该模型还可以用作小鼠替代品，以改进实验并简化设置，减少动物处于麻醉或固定状态的时间。根据文献检索，在过去5年中，约有1300只小鼠用于质子研究，但随着质子束技术的广泛应用，这一数字将上升。定期使用该工具测量剂量输出并识别任何问题将增加结果的置信度，从而减少获得统计学显著性数据所需的动物数量，并改进剂量输送以最大限度地降低潜在毒性。