Small Animal Radiation Research Platform with Cone-beam CT Guidance

描述（申请人提供）：弗吉尼亚大学医学院目前有一台过时的40年历史的正电压x射线机，用于小动物的照射。本提案是用最先进的小动物辐射研究平台（SARRP）辐射器取代我们过时的辐射器。除了在体外提供辐射外，SARRP是第一个将准直，精确剂量建模和3D体积成像引导集成到单个平台中的系统，从而允许在动物中实现高度适形的剂量分布。SARRP提供了一个重要的工具，将我们推向小分子、放射和免疫治疗协同使用的时代。辐射是对抗大多数实体瘤最有效的手段。最近在辐射物理学方面的改进已经导致了辐射传输的显著改进，使得辐射剂量的空间靶向变得更加精确。然而，不断增加的空间靶向剂量对大多数实体瘤的局部控制率只有很小的影响。放疗的一个关键优势是，与所有化疗和所有分子靶剂相比，放疗不会引起耐药性。因此，将空间靶向放射治疗与旨在增强肿瘤细胞杀伤的分子靶向药物相结合，具有提高实体瘤局部控制率的巨大潜力。事实上，在放射肿瘤科接受治疗的大多数患者都采用放射和化疗的结合治疗或分子靶向治疗。确定与辐射联合使用的最佳药物以及确定药物/辐射相互作用的机制基础需要使用聚焦辐射进行临床前研究，以模拟实际的临床治疗。具有这些功能的辐照器的可用性将刺激弗吉尼亚大学癌症中心在神经肿瘤学和前列腺癌的特定领域以及DNA损伤反应的广泛领域正在研究的特定药物的研究。由于第一阶段的研究证明是成功的，我们预计将在妇科、肺癌和胃肠道癌症以及更广泛的癌症中使用。除了肿瘤学研究外，SARRP还将促进免疫学和心血管疾病领域的研究。UVA的协作和交流环境将确保在广泛的适应症中快速采用SARRP方法。

DESCRIPTION (provided by applicant): The University of Virginia School of Medicine currently has an obsolete 40-year-old orthovoltage XRAY machine which is used for irradiation of small animals. This proposal is to replace our obsolete irradiator with a state of the art small animal radiation research platform (SARRP) irradiator. In addition to delivering radiation in vitro, SARRP is the first system that integrates collimation, accurate dose modeling and 3D volumetric imaging guidance into a single platform thereby allowing highly conformal dose distributions to be achieved in animals. The SARRP provides an important tool in moving us to the era where small molecules, radiation, and immunotherapy are used synergistically. Radiation is the most active agent against most solid tumors. Recent improvements in radiation physics have led to dramatic improvements in radiation delivery, allowing elegant spatial targeting of the radiation dose. However, escalating spatially targeted doses has had only minimal impact on the local control rates of most solid tumors. One key advantage of radiation is that in contrast to essentially all chemotherapeutic and all molecular target agents, radiation does not induce resistance. Therefore, coupling spatially targeted radiation therapy with molecularly targeted agents designed to enhance tumor cell kill holds tremendous potential to improve local control rates of solid tumors. Indeed most patients treated in Radiation Oncology Departments for cure are treated with a combination of radiation and chemotherapy or molecularly targeted therapy. Identifying the optimal agents to use in combination with radiation as well as defining the mechanistic basis of drug/radiation interactions requires preclinical studies using focused radiation in order to mimic actual clinical treatments. The availability of an irradiator with these capabilities will stimulate such studies testing specific agents currently under investigation at the University of Virginia Cancer Center in the specific areas of neuro-oncology and prostate cancer as well as in the broad area of DNA damage response. As the first tier of investigations prove successful, we anticipate use in gynecologic, lung, and GI cancers and more generally. In addition to oncologic investigations, the SARRP will also facilitate research in the areas of immunology and cardiovascular diseases. The collaborative and communicative environment at UVA will ensure the rapid adoption of SARRP approach in a wide array of indications.