Towards a novel small animal proton irradiation platform: the SIRMIO project

<b>Background:</b> Precision small animal radiotherapy research is a young emerging field aiming to provide new experimental insights into tumor and normal tissue models in different microenvironments, to unravel complex mechanisms of radiation damage in target and non-target tissues and assess efficacy of novel therapeutic strategies. For photon therapy, modern small animal radiotherapy research platforms have been developed over the last years and are meanwhile commercially available. Conversely, for proton therapy, which holds potential for an even superior outcome than photon therapy, no commercial system exists yet. <b>Material and methods:</b> The project SIRMIO (Small Animal Proton Irradiator for Research in Molecular Image-guided Radiation-Oncology) aims at realizing and demonstrating an innovative portable prototype system for precision image-guided small animal proton irradiation, suitable for installation at existing clinical treatment facilities. The proposed design combines precise dose application with <i>in situ</i> multi-modal anatomical image guidance and <i>in vivo</i> verification of the actual treatment delivery. <b>Results and conclusions:</b> This manuscript describes the status of the different components under development, featuring a dedicated beamline for degradation and focusing of clinical proton beams, along with novel detector systems for <i>in situ</i>imaging and range verification. The foreseen workflow includes pre-treatment proton transmission imaging, complemented by ultrasonic tumor localization, for treatment planning and position verification, followed by image-guided delivery with <i>on site</i> range verification by means of ionoacoustics (for pulsed beams) and positron-emission-tomography (PET, for continuous beams). The proposed compact and cost-effective system promises to open a new era in small animal proton therapy research, contributing to the basic understanding of <i>in vivo</i> radiation action to identify areas of potential breakthroughs for future translation into innovative clinical strategies.

**背景：** 精准小动物放射治疗研究是一门新兴前沿领域，旨在为不同微环境下的肿瘤与正常组织模型提供全新实验视角，阐明靶组织与非靶组织辐射损伤的复杂机制，并评估新型治疗策略的疗效。光子治疗领域中，近年来已开发出成熟的小动物放射治疗研究平台，并已实现商业化应用。而相比光子治疗具备更优治疗潜力的质子治疗，目前尚无商用系统问世。
**材料与方法：** SIRMIO项目（Small Animal Proton Irradiator for Research in Molecular Image-guided Radiation-Oncology）旨在研发并验证一款创新便携式原型系统，用于精准影像引导下的小动物质子辐照，可适配现有临床治疗设施的安装需求。本设计将精准剂量递送与原位（in situ）多模态解剖影像引导，以及实际治疗实施的在体（in vivo）验证相结合。
**结果与结论：** 本手稿阐述了各研发组件的当前进展，其中包含用于临床质子束降级与聚焦的专用束线，以及用于原位（in situ）成像和射程验证的新型探测器系统。预设的工作流程涵盖治疗前质子透射成像，并辅以超声肿瘤定位，用于治疗计划与位置验证；随后开展影像引导的辐照递送，并通过离子声学（适用于脉冲束流）与正电子发射断层扫描（PET，适用于连续束流）实现现场（on site）射程验证。这款紧凑且具成本效益的系统有望开启小动物质子治疗研究的新纪元，助力人们加深对在体（in vivo）辐射作用机制的基础认知，从而识别潜在的突破性研究方向，为未来转化为创新临床治疗策略提供支撑。