EFFECTS OF NONUNIFORM DISTRIBUTIONS OF RADIOACTIVITY

放射性不均匀分布的影响

• 批准号: 6751565
• 负责人: Roger W. Howell
• 金额: $ 24.73万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6751565
• 关键词: cell line; radiation sensitivity; radiation therapy dosage; radiobiology; radionuclide therapy; radiopharmacology; tissue /cell culture

There are numerous factors that determine the biological response of tissues that contain radioactivity such as radiosensitivity, distribution of radioactivity, type and number of radiations emitted by the radionuclide, biokinetics of the radionuclide, repair time, etc. Traditionally, the mean absorbed dose to the tissue is calculated to correlate the biological response with mean absorbed dose. However, nonuniform activity distributions in tissue at the multicellular and subcellular levels result in nonuniform doses and therefore have made it difficult to adequately correlate biological response with mean absorbed dose. This is an important problem in diagnostic and therapeutic nuclear medicine. In the case of diagnosis, the risk of the radiation insult can in principle be drastically underestimated and potentially lead to increased risk of inducing cancer. In contrast, patients can be over- or under-treated in radionuclide therapy of cancer. Over-treatment or under-treatment in radionuclide therapy of cancer can have very adverse consequences in the final outcome for the patient. While calculation of absorbed dose at the cellular level has been advocated as a means to address this problem, this has largely remained a theoretical exercise. The applicants hypothesize that the biological response of tissues containing incorporated radionuclides can be correlated with absorbed dose when calculated at the cellular level. To test the hypothesis, a novel in vitro multicellular cluster model will be used which allows tight control over variables. Multicellular clusters will be assembled with mammalian cells containing radioactivity and the cell survival fraction as a function of cluster activity will be determined for several different radiopharmaceuticals which emit alpha particles, beta particles, or Auger electrons. Different percentages of the cells will be labeled with the different radiochemicals to ascertain the impact of nonuniform distributions of radioactivity at the cellular and subcellular levels. By controlling the percentage of cells labeled, this model will also be used to ascertain the role of bystander effects in the biological effects of incorporated radioactivity. These data and cellular dosimetry calculations will be used to develop a theoretical model to predict response based on cellular absorbed dose and bystander effects. The outcome of this research is expected to have a major impact on understanding and predicting the biological response of tumor and normal tissue to nonuniform distributions of radioactivity.

决定生物反应的因素有很多 含有放射性的组织，例如放射敏感性，分布 放射性、放射性核素发射的辐射类型和数量， 放射性核素的生物动力学、修复时间等。传统上，平均值 计算组织吸收剂量以关联生物反应 与平均吸收剂量。然而，组织中的活性分布不均匀 在多细胞和亚细胞水平上导致剂量不均匀 因此很难充分关联生物反应 与平均吸收剂量。这是诊断和治疗中的一个重要问题 治疗性核医学。在诊断的情况下，风险 原则上，辐射损伤可能会被大大低估，并且有可能 导致诱发癌症的风险增加。相比之下，患者可能会过度 或在癌症的放射性核素治疗中治疗不足。过度治疗或 癌症放射性核素治疗中治疗不足可能会产生非常不利的影响 对患者的最终结果产生影响。同时计算 提倡将细胞水平的吸收剂量作为解决问题的方法 这个问题在很大程度上仍然是一个理论练习。申请人 假设含有掺入物的组织的生物反应 当计算时，放射性核素可以与吸收剂量相关 细胞水平。为了检验这一假设，一种新型的体外多细胞簇 将使用允许严格控制变量的模型。多细胞 簇将与含有放射性的哺乳动物细胞组装在一起 细胞存活分数作为簇活性的函数将被确定 对于发射α粒子、β粒子的几种不同放射性药物 粒子，或俄歇电子。不同百分比的细胞将 用不同的放射化学物质标记以确定不均匀的影响 细胞和亚细胞水平的放射性分布。经过 控制标记细胞的百分比，该模型也将用于 确定旁观者效应在生物效应中的作用 并入放射性。这些数据和细胞剂量测定计算将 用于开发理论模型来预测基于细胞的反应 吸收剂量和旁观者效应。这项研究的结果是预期的 对理解和预测生物反应产生重大影响 肿瘤和正常组织的放射性分布不均匀。