Preclinical radiotherapy studies using mouse models are an indispensable step on the path from in vitro experiments to clinical implementation. In support of this step, dedicated small animal irradiators have been developed to provide a platform for testing new radiation strategies for cancer treatment. Although some systems offer an advanced setup including high resolution positioning and imaging, the investment in obtaining, maintaining, and using small animal irradiators is substantial both monetary and in man-hours. An alternative approach is to use linear accelerators (LINACs) designed for irradiation of humans and widely available in clinical environments, as they may potentially increase quality and translational value of preclinical cancer research.

Here we present a simple setup for fast and localized irradiation of subcutaneous mouse flank tumors using a clinical 10 MV flattening filter free (FFF) LINAC beam. Alanine pellet dosimeters were used for validation of the setup. Good agreement was found between alanine and the vertical Eclipse dose profile both outside and inside the field. Additionally, the alanine pellets verified the in vivo dose to the mouse tumor location by comparing and finding agreement between the dose from ten subcutaneously inserted dosimeters and ten externally placed dosimeters. Finally, the setup was tested using the syngeneic CT26 colon cancer mouse model. A single dose of 15 Gy was provided to subcutaneous tumors on the right flank. Comparison of tumor growth between the irradiated and non-irradiated tumors showed a delay in tumor growth and improved overall survival amongst the irradiated mice.

This study demonstrates that clinical LINACs are an easy, fast, and cost effective alternative to small animal irradiators without compromising accurate dose delivery. Clinical LINACs could be utilized to a greater extent in preclinical studies.

使用小鼠模型进行临床前放疗研究是从体外实验到临床实施过程中不可或缺的一步。为了支持这一步骤，已经开发出专用的小动物辐照器，为测试癌症治疗的新辐射策略提供平台。尽管一些系统提供了包括高分辨率定位和成像在内的高级设置，但在获取、维护和使用小动物辐照器方面的投资无论是金钱还是工时都是巨大的。另一种方法是使用直线加速器 (LINAC)，该直线加速器专为人体照射而设计，可在临床环境中广泛使用，因为它们可能会提高临床前癌症研究的质量和转化价值。

在这里，我们展示了一个简单的设置，用于使用临床 10 MV 扁平无过滤器 (FFF) LINAC 光束对皮下小鼠侧腹肿瘤进行快速和局部照射。丙氨酸颗粒剂量计用于验证设置。在场外和场内，丙氨酸和垂直 Eclipse 剂量分布之间都发现了良好的一致性。此外，丙氨酸颗粒验证了体内通过比较和发现来自十个皮下插入剂量计和十个外部放置的剂量计的剂量之间的一致性，对小鼠肿瘤位置的剂量进行了比较。最后，使用同基因 CT26 结肠癌小鼠模型对设置进行了测试。向右侧皮下肿瘤提供 15 Gy 的单剂量。辐照和未辐照肿瘤之间肿瘤生长的比较显示肿瘤生长延迟并提高了受辐照小鼠的总体存活率。

这项研究表明，临床 LINAC 是一种简单、快速且具有成本效益的替代小动物辐照器的方法，而且不会影响准确的剂量输送。临床 LINAC 可以在临床前研究中得到更大程度的利用。