Spatial-Temporal Imaging of Cell Proliferation & Hypoxia

细胞增殖的时空成像

• 批准号: 7036115
• 负责人: ROBERT JERAJ
• 金额: $ 16.54万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-26 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036115
• 关键词: cell proliferation; hypoxia; molecular /cellular imaging; neoplasm /cancer; neoplasm /cancer therapy

DESCRIPTION (provided by applicant): From our preliminary studies, in which we followed spatial-temporal distribution of cell proliferation through the course of radiation treatment, tumor heterogeneity was detected before the treatment. In addition, a significant re-distribution of the proliferative capacity was observed in the tumor during the treatment, including significant and unexpected accelerated repopulation. Advances in radiation treatment delivery, such as intensity-modulated radiotherapy, provide the ability to customize radiation delivery based on physical conformity. Incorporation of regional biologic information, especially its changes during therapy, could lead to treatment adaptation. Similarly, early assessment of chemotherapy efficacy and lead to improved cancer management. The spatio-temporal response represents significant challenges for image-guided interventions; and the potential for significant improvement of the current treatment practice. Quantification of the changes and better understanding of tumor kinetics are the main unknowns preventing treatment adaptation. Our research will be focused in these two areas. Our main goals in this project are: 1) to estimate inter- and intra-tumor heterogeneity of cell proliferation and hypoxia for two tumor types and quantify its spatio-temporal change during cancer therapy and 2) to develop and test the methodology for quantitative monitoring of spatio- temporal cell proliferation and hypoxia distribution in the tumor and surrounding critical structures during cancer therapy. FLT will be used as a proliferation marker and Cu-ATSM as a hypoxia marker for in-vivo PET imaging. The PET imaging results will be correlated to immunohistochemical analyses of selected biopsy samples to further validate the used radiopharmaceuticals. Advanced image co-registration techniques (e.g., rigid body, deformable registration) and spatial statistics methods (e.g., Moran, G statistics) will be developed and applied to establish appropriate level of image and data analyses. Our methodology will be developed on larger animal tumor models (dogs), which are an excellent research model due to its large size and biological similarity to humans. Two spontaneous dog tumor types - soft tissue sarcoma (treated with radiotherapy) and non-Hodgkin's lymphoma (treated with chemotherapy) will be investigated. In addition to proving J feasibility, the data collected in this pilot study will be used to perform well-grounded power calculations for a future larger study and translation to humans. By combining concurrent monitoring of proliferation and hypoxia (FLT/Cu-ATSM) distributions and advanced image analyses, we hypothesize that spatio-al temporal quantification of the magnitude, and the change of both parameters, can provide quantitative basis for molecular image guidance of cancer therapy.

描述（由申请人提供）：根据我们的初步研究，我们在辐射治疗过程中遵循细胞增殖的时空分布，在治疗前检测到肿瘤异质性。此外，在治疗过程中观察到在肿瘤中观察到增殖能力的显着重新分布，包括明显的和意外的加速重生。辐射治疗递送的进步，例如强度调节放射疗法，可以根据身体一致性自定义辐射输送。纳入区域生物学信息，尤其是其在治疗过程中的变化，可能会导致治疗适应。同样，早期评估化​​学疗法功效并导致癌症管理的改善。时空响应代表了图像引导的干预措施的重大挑战。以及显着改善当前治疗实践的潜力。量化变化和更好地理解肿瘤动力学是预防治疗适应的主要未知数。我们的研究将集中在这两个领域。我们在该项目中的主要目标是：1）估计两种肿瘤类型的细胞增殖和缺氧的肿瘤内和肿瘤内异质性，并量化其在癌症治疗期间的时空变化和2），以开发和测试用于定量监测临时细胞增殖和低氧在肿瘤和周围癌症治疗过程中的临时细胞增殖和低氧分布的方法。 FLT将用作增殖标记和CU-ATSM作为体内宠物成像的缺氧标记。 PET成像结果将与选定活检样品的免疫组织化学分析相关，以进一步验证使用的放射性药物。将开发并应用高级图像共同注册技术（例如，刚体，可变形的注册）和空间统计方法（例如，Moran，G统计数据），以建立适当的图像和数据分析水平。我们的方法将在较大的动物肿瘤模型（Dogs）上开发，该模型是一种出色的研究模型，因为它与人类的大小和生物学相似。将研究两种自发的狗肿瘤类型 - 软组织肉瘤（接受放射治疗）和非霍奇金淋巴瘤（用化学疗法治疗）。除了证明可行性外，该试点研究中收集的数据还将用于对未来的更大研究和转化为人类进行良好的功率计算。通过将同时监测增殖和缺氧（FLT/CU-ATSM）分布和高级图像分析相结合，我们假设大小的时空时间定量以及两个参数的变化可以为癌症治疗的分子图像指导提供定量基础。