Small Animal Radiation Research Platform with Cone-beam CT Guidance

锥束CT引导小动物放射研究平台

• 批准号: 7795538
• 负责人: James M Larner
• 金额: $ 49.89万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-10 至 2010-12-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795538
• 关键词: Adoption; Animals; Area; Arts; Cardiovascular Diseases; Clinical Treatment; Collimator; Coupling; DNA Damage; Dose; Ensure; Environment; Gynecologic; Image; Immunology; Immunotherapy; In Vitro; Investigation; Lung; Malignant Neoplasms; Malignant neoplasm of prostate; Molecular Target; Patients; Pharmaceutical Preparations; Radiation; Radiation Interaction; Radiation Oncology; Radiation Physics; Radiation therapy; Research; Resistance; Roentgen Rays; Solid Neoplasm; System; Testing; Universities; University of Virginia Cancer Center; Virginia; base; cell killing; chemotherapy; cone-beam computed tomography; design; improved; irradiation; medical schools; neoplastic cell; neuro-oncology; preclinical study; response; small molecule; three-dimensional modeling; tool

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.

描述（申请人提供）： 弗吉尼亚大学医学院目前有一台已经过时的 40 年历史的正电压 X 射线机，用于对小动物进行照射。该提案旨在用最先进的小动物辐射研究平台 (SARRP) 辐照器取代我们过时的辐照器。除了在体外提供辐射外，SARRP 还是第一个将准直、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，从而可以在动物中实现高度适形的剂量分布。 SARRP 提供了一个重要工具，帮助我们进入小分子、放射和免疫疗法协同使用的时代。放射线是对​​抗大多数实体瘤最有效的药物。辐射物理学的最新进展极大地改善了辐射传输，从而实现了辐射剂量的优雅空间定位。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影响很小。辐射的一个关键优点是，与基本上所有化疗药物和所有分子靶向药物相比，辐射不会诱发耐药性。因此，将空间靶向放射治疗与旨在增强肿瘤细胞杀伤力的分子靶向药物相结合，对于提高实体瘤的局部控制率具有巨大的潜力。事实上，大多数在放射肿瘤科接受治疗的患者都接受放射和化疗联合治疗或分子靶向治疗。确定与放射组合使用的最佳药物以及定义药物/放射相互作用的机制基础需要使用聚焦放射进行临床前研究，以模拟实际的临床治疗。具有这些功能的辐照器的出现将刺激此类研究，测试弗吉尼亚大学癌症中心目前正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中研究的特定药物。随着第一层研究的成功，我们预计可用于妇科癌症、肺癌和胃肠道癌症以及更广泛的癌症。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 SARRP 方法在广泛的适应症中得到快速采用。