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.

有许多因素决定生物学反应 包含放射性的组织，例如放射性敏感性，分布 放射性核素发出的放射性，类型和数量， 放射性核素，维修时间等的生物动力学。传统上是平均值 计算吸收到组织的剂量以使生物反应相关 平均吸收剂量。但是，组织中的非均匀活性分布 在多细胞和亚细胞水平下，会导致不均匀剂量 因此，很难充分地关联生物学反应 平均吸收剂量。这是诊断和 治疗核医学。在诊断的情况下， 辐射侮辱原则上可以被大大低估，并可能被低估 导致诱导癌症的风险增加。相反，患者可能过度 或在癌症的放射性核素治疗中治疗。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 患者最终结果的后果。而计算 在细胞水平上吸收的剂量已被提倡作为解决的手段 这个问题，这在很大程度上仍然是理论上的练习。申请人 假设含有融合的组织的生物学反应 当在 细胞水平。为了检验假设，一种新型的体外多细胞簇 将使用模型，允许对变量进行严格的控制。多细胞 簇将与含有放射性的哺乳动物细胞组装 将确定细胞存活分数作为聚类活性的函数 对于发射α颗粒的几种不同的放射性药物，beta 颗粒或螺旋钻电子。不同百分比的细胞将是 标记不同的放射性化学物质以确定不均匀的影响 放射性在细胞和亚细胞水平上的分布。经过 控制标记的单元格的百分比，该模型也将用于 确定旁观者效应在生物学作用中的作用 结合放射性。这些数据和细胞剂量测定计算将 用于开发一个理论模型以预测基于细胞的响应 吸收剂量和旁观者的作用。预计这项研究的结果 对理解和预测生物学反应产生重大影响 肿瘤和正常组织至放射性分布。