Imaging Lung Cancer in Mice To Improve Radiation Therapy

对小鼠肺癌进行成像以改善放射治疗

• 批准号: 7105544
• 负责人: David Guy Kirsch
• 金额: $ 13.71万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-03 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105544
• 关键词: apoptosis; bioimaging /biomedical imaging; biological models; bioluminescence; computed axial tomography; genetically modified animals; laboratory mouse; lung imaging /visualization /scanning; magnetic resonance imaging; model design /development; neoplasm /cancer blood supply; neoplasm /cancer diagnosis; neoplasm /cancer radiation therapy; neoplastic process; nonhuman therapy evaluation; nonsmall cell lung cancer; p53 gene /protein; tissue /cell culture

DESCRIPTION (provided by applicant): Recent advances in small animal imaging and the development of more accurate mouse models of human cancer provide exciting opportunities to improve radiation therapy for patients with lung cancer. The goal of this project is to elucidate molecular mechanisms of lung tumor biology following radiation therapy. Lung adenocarcinomas in mice will be imaged with X-ray computed tomography (CT) and magnetic resonance imaging (MRI) to dissect the cellular and genetic requirements for tumor response to radiation therapy. Cre-lox technology will be used to generate lung cancers with specific gene mutations. In addition, lung tumors will be produced with cell death pathways that are disrupted in tumor cells or in tumor stroma. The response of the tumors to radiation therapy will be compared by CT. These studies will clarify the role of the tumor suppressor gene p53 in the response of lung cancers to radiation therapy, determine whether apoptosis of tumor cells is required for radiation therapy to eradicate lung cancers, and identify the cellular target for radiation therapy. The vascular volume fraction of tumors will be measured with MRI and will be correlated to tumor response after irradiation. In addition, luciferase reporters that are activated during apoptosis will be optimized in cells grown in tissue culture. These reporters will be used to generate transgenic mice to develop a mouse model for in vivo bioluminescence imaging (BLI) of apoptosis. Imaging lung cancer in mice with CT, MRI, and BLI will reveal key mechanisms of how lung cancer responds to radiation therapy. The picture created from these imaging studies will ultimately form the foundation for improved treatment of patients with lung cancer.

描述（由申请人提供）：小动物成像的最新进展和更准确的人类癌小鼠模型的发展为改善肺癌患者的放射治疗提供了令人兴奋的机会。该项目的目的是阐明放射治疗后肺肿瘤生物学的分子机制。小鼠中的肺腺癌将通过X射线计算机断层扫描（CT）和磁共振成像（MRI）成像，以剖析肿瘤对放射治疗的肿瘤反应的细胞和遗传要求。 Cre-Lox技术将用于产生具有特定基因突变的肺癌。另外，将使用在肿瘤细胞或肿瘤基质中破坏的细胞死亡途径产生肺肿瘤。 CT将比较肿瘤对放射治疗的反应。这些研究将阐明肿瘤抑制基因p53在肺癌对放射治疗的反应中的作用，确定放射治疗是否需要肿瘤细胞的凋亡才能消除肺癌，并确定辐射疗法的细胞靶标。肿瘤的血管体积分数将用MRI测量，并在照射后与肿瘤反应相关。另外，在组织培养物中生长的细胞中，在凋亡过程中被激活的荧光素酶报告器将优化。这些记者将用于生成转基因小鼠，以开发凋亡的体内生物发光成像（BLI）的小鼠模型。 使用CT，MRI和BLI的小鼠中的肺癌成像将揭示肺癌如何应对放射治疗的关键机制。这些成像研究创建的图片最终将构成改善肺癌患者治疗的基础。