Image-Guided Radiation Therapy and Radiosurgery for Small Animals

描述（由申请人提供）：放射治疗用于治疗大约50%的癌症患者。为了提高放射治疗的治愈率，减少放射的短期和长期副作用，我们已经获得了NIH的多项资助，用于研究小动物的放射生物学。尽管在靶标定位和辐射输送方面的重大技术进步已经在临床中出现，但这项技术在杜克大学还无法用于我们的临床前实验。无法获得放射目标（肿瘤或正常器官）的图像并将辐射传递到聚焦的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中开展临床有意义的研究的能力，我们要求一种结合多种机载成像功能的共享仪器，如micro-CT和适形小束放射治疗。这项技术现在被用于图像引导放射治疗。该仪器采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。我们建议利用这项技术来研究(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，以高精度和准确性安全地提供大剂量辐射，以解剖肿瘤控制机制。这种方法将使我们能够研究有临床意义的肿瘤治愈终点。此外，在每次治疗前对小动物进行成像和定位肿瘤靶点的能力将有助于小动物的分级放射治疗计划，这在临床上通常用于治疗患者。该仪器还将使我们拥有前所未有的能力，将放射治疗集中在单个器官上，甚至是器官的一部分，以研究正常组织损伤的机制。该方法可避免放射治疗造成的多器官损伤，从而为小动物放射诱导的正常组织损伤的研究提供了便利。总之，这项技术极大地提高了我们研究基本放射生物学问题的能力，使用的技术与我们治疗病人的技术相同。将这种新型仪器与杜克大学辐射生物学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.