Image-Guided Radiation Therapy and Radiosurgery for Small Animals

描述（由申请人提供）：放射治疗用于治疗约50%的癌症患者。为了提高放射治疗的治愈率并减少放射的短期和长期副作用，我们获得了NIH的多项赠款，用于研究小动物的放射生物学。尽管在临床中靶点定位和放射治疗方面已经取得了重大的技术进步，但在杜克大学，我们的临床前实验中还没有这项技术。无法获得放射靶（肿瘤或正常器官）的图像并将放射传递到聚焦体积一直是推进放射肿瘤学研究的主要障碍。为了提高我们在放射生物学领域开展有临床意义的研究的能力，我们需要一种共享仪器，该仪器将多种机载成像功能（如微型CT）与适形小束放射治疗相结合。这项技术现在正被用于通过图像引导放射治疗来治疗患者。拟议的仪器使用最先进的小动物技术，严格模拟我们患者的计划和治疗条件。我们建议使用该技术研究（1）肿瘤控制机制和（2）放射治疗对正常组织的损伤。我们将利用机载成像和定制准直器安全地提供高精度和准确度的大剂量辐射，以剖析肿瘤控制机制。这种方法将使我们能够研究肿瘤治愈的临床意义终点。此外，在每次治疗之前对小动物进行成像并定位肿瘤靶点的能力将有助于小动物的分次放射治疗计划，这通常用于治疗临床患者。该仪器还将使我们具有前所未有的能力，将放射治疗集中在单个器官，甚至是器官的一部分，以研究正常组织损伤的机制。这种方法将避免多器官损伤的辐射治疗，从而有利于研究辐射诱导的正常组织损伤的小动物。总之，这项技术极大地提高了我们使用与治疗患者相同的技术研究基本放射生物学问题的能力。将这种新型仪器与杜克在放射生物学方面的广泛专业知识相结合，将带来新的发现，并将促进它们转化为改进的癌症治疗。

DESCRIPTION (provided by applicant): Radiation therapy is used to treat approximately 50% of all patients with cancer. To improve the cure rate with radiation therapy and to decrease the short- and long-term side effects of radiation, we have received multiple NIH grants to study radiation biology in small animals. Although major technological improvements in target localization and radiation delivery have occurred in the clinic, this technology is not available at Duke University for our pre-clinical experiments. The inability to obtain images of the radiation target (tumor or normal organ) and to deliver radiation to a focused volume has been a major barrier to advancing radiation oncology research. To improve our ability to carry out clinically meaningful research in radiation biology, we request a shared instrument that combines multiple on-board imaging capabilities, such as micro-CT, with conformal small beam radiation therapy. This technology is now being used to treat patients with image-guided radiation therapy. The proposed instrument uses state-of-the-art technology for small animals that rigorously simulates the planning and treatment conditions of our patients. We propose to use this technology to investigate (1) mechanisms of tumor control and (2) normal tissue injury by radiation therapy. We will utilize the on-board imaging and the custom collimators to safely deliver large doses of radiation with high precision and accuracy to dissect mechanisms of tumor control. This approach will allow us to study the clinically meaningful endpoint of tumor cure. Moreover, the ability to image small animals and localize the tumor target before each treatment will facilitate fractionated radiation therapy schedules for small animals, which are routinely used to treat patients in the clinic. The instrument will also allow us to have the unprecedented ability to focus radiation therapy on a single organ, or even part of an organ, to study mechanisms of normal tissue injury. This approach will avoid multi-organ injury by the radiation treatment and will thereby facilitate studies of radiation-induced normal tissue injury in small animals. In summary, this technology offers a dramatic improvement in our ability to study fundamental radiation biology questions using the same technology with which we treat patients. Combining this novel instrument with the extensive expertise in radiation biology at Duke will bring about new discoveries and will facilitate their translation into improved cancer therapy.