EFFECTS OF NONUNIFORM DISTRIBUTIONS OF RADIOACTIVITY

放射性不均匀分布的影响

• 批准号: 6604168
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6604168
• 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很多。 对于含有放射性的组织，如辐射敏感性，分布 放射性、放射性核素发出的辐射的类型和数量， 放射性核素的生物动力学、修复时间等。传统上，平均 对组织的吸收剂量的计算是为了关联生物反应 平均吸收剂量。然而，组织中不均匀的活性分布 在多细胞和亚细胞水平上导致剂量不均匀和 因此很难将生物反应充分地关联起来 平均吸收剂量。这是诊断和分析中的一个重要问题 治疗性核医学。在诊断的情况下， 原则上，辐射侮辱可能被严重低估，并有可能 导致致癌风险增加。相比之下，病人可能会过度- 或在癌症的放射性核素治疗中未得到充分治疗。过度治疗或 在癌症的放射性核素治疗中，治疗不足可能会有非常不利的影响 患者的最终结果中的后果。在计算时 细胞水平的吸收剂量一直被认为是一种解决 这个问题，这在很大程度上仍然是一个理论练习。申请者 假设含有掺入物的组织的生物反应 计算时，放射性核素可与吸收剂量相关。 细胞水平。为了验证这一假设，一种新的体外多细胞簇 将使用允许对变量进行严格控制的模型。多蜂窝 集群将与含有放射性的哺乳动物细胞组装在一起 将确定作为簇活动函数的细胞存活率 对于发射α粒子的几种不同的放射性药物， 粒子，或俄歇电子。不同百分比的细胞将被 用不同的放射性化学物质标记以确定不均匀的影响 放射性在细胞和亚细胞水平的分布。通过 控制标记细胞的百分比，该模型还将用于 确定旁观者效应在生物效应中的作用 加入放射性物质。这些数据和蜂窝剂量学计算将 用于开发基于元胞的响应预测的理论模型 吸收剂量和旁观者效应。这项研究的结果是令人期待的 对理解和预测生物反应有重大影响 肿瘤和正常组织的放射性分布不均匀。