Development of a multipurpose small animal phantom for pre-clinical radiotherapy studies

该项目的最初目标是为临床前放射生物学研究建立商业剂量测定服务，这将i)通过提供最先进的剂量测定来改善实验数据和准确性，ii)减少使用的动物总数，iii)为放射致敏剂的研究提供一个新的基于3D组织的平台。这将通过标准化剂量测定方案的开发来实现，该方案将减少剂量不确定性，并开发多用途小动物模型。目前，英国各地有许多不同的辐照单位使用自己的剂量测定表，因此，作为建立新服务的一部分，将对目前的做法进行全面审计。由于辐射研究中的剂量反应剧烈，剂量不确定性降低5%将使达到相同统计相关性所需的动物数量减少大约一半。放射生物学研究标准和质量保证程序的定义将有助于规范临床前放射治疗活动。这将增加临床研究人员和资助机构对这些方法的信心，并为国家物理实验室（NPL）提供的剂量测定服务开辟新的市场机会。拟议的用于临床前成像的新剂量测定服务将缩小临床中已建立的方法，为临床前工作提供信心和准确性，使后者达到与现有患者提供的相同标准。作为x射线设备的主要供应商，Xstrahl有限公司将受益于放射生物学研究的增加，因为进入的经济和方法障碍降低了。一种独特类型的假体也将被开发出来，它能够容纳一个定制的微流体装置，包含组织活检，这将为辐射药物协同研究提供另一种类似体内的选择。幻影将包含来自异种移植模型或人体活检的组织切片，例如4mm x 4mm x 0.2mm，然后可以在精确控制的条件下使用这些切片来测量有或没有药物照射的效果。此外，这些组织研究将纳入所有改进的剂量学测量，从而显着提高实验准确性。该项目解决了研究机构、资助机构和临床社区确定的问题，为国家物理实验室开辟了新的商业机会，为Xstrahl有限公司提供了技术改进，为赫尔大学提供了许可或衍生选择。

The initial aim of the project is to establish a commercial dosimetry service for pre-clinical radiobiology studies which will i)improve the data and accuracy of experiments via provision of state of the art dosimetry, ii) reduce the total number ofanimals used and iii) provide a novel 3D tissue-based platform for study of radiosensitizers.This will be achieved through the development of standardized dosimetry protocols that will reduce dose uncertainties, andthe development of a multipurpose small animal phantom. A number of different irradiation units are currently employedacross the UK using their own dosimetry schedules, therefore as part of establishing the new service a comprehensiveaudit of current practices will be undertaken. Due to the steep dose responses in radiation studies a 5% reduction in doseuncertainty would roughly halve the number of animals required to achieve the same statistical relevance. The definition ofstandards and quality assurance procedures for radiobiological studies will help regulate preclinical radiotherapy activities.This will increase the confidence of clinical researchers and the funding bodies in such methods, as well as opening newmarket opportunities for dosimetry services offered by the National Physics Laboratory (NPL). The proposed newdosimetry service for pre-clinical imaging will scale-down established methodologies from the clinical to provide confidenceand accuracy for pre-clinical work, bringing the latter up to the same standard as the existing provision for patients. As amajor supplier of x-ray equipment, Xstrahl Ltd will benefit from an increase in radiobiological studies as the economic andmethodological barriers to entry are lowered.A unique type of phantom will also be developed that is capable of housing a bespoke microfluidic device, containing atissue biopsy that will offer an alternative in vivo-like option for radiation-drug synergistic studies. The phantom will containtissues slices, e.g. 4mm x 4mm x 0.2mm from xenograft models or human biopsies and these can then be used tomeasure the effects of irradiation with or without drugs, under precisely controlled conditions. Furthermore these tissue studies will incorporate all the improved dosimetry measurements thus significantly improving the experimental accuracy.The project addresses issues identified by research organisations, funding bodies and the clinical community and opens upnew business opportunities for NPL, improvements in technology for Xstrahl Ltd and licensing or spin-out options for theUniversity of Hull.