Institute for Radiation Research, Karlsruhe Institute of Technology, P.O. Box 3640, D-76021 Karlsruhe, Germany.
Health Phys. 2010 Oct;99(4):547-52. doi: 10.1097/HP.0b013e3181bfba02.
Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS.
二乙烯三胺五乙酸（DTPA）用于钚的去污染，因为已知它能够在治疗后几天内通过形成稳定的 Pu-DTPA 复合物来增强其尿液排泄。去污染可防止在器官中积累，从而带来剂量学效益，而使用现有模型从生物测定数据中很难定量计算。作为欧洲辐射剂量学协调网络（CONRAD）的一项任务，启动了一个描述通过给予 DTPA 进行锕系元素去污染的生物动力学机制的生物动力学模型的开发。Leggett 等人的系统生物动力学模型和国际辐射防护委员会出版物 53 的 DTPA 化合物的生物动力学模型是起点。该小组提出了一种基于文献中 14C 标记 DTPA 研究的生理学解释的新的给予 DTPA 的生物动力学模型。钚和 DTPA 的生物动力学分别建模。通过描述钚原子和 DTPA 分子与 Pu-DTPA 复合物的螯合过程的二阶动力学过程将系统连接起来。假设螯合仅发生在血液中和系统隔室 ST0（代表快速周转的软组织）中，并且 Pu-DTPA 复合物和给予的 DTPA 形式具有相同的生物动力学行为。CONRAD 方法的首次应用表明，给予 DTPA 后钚的尿液排泄增强强烈受螯合速率常数的影响。将其设置为高值可很好地拟合观察到的数据。但是，该模型还不能令人满意，因为无法以现实的方式预测在短时间内重复给予 DTPA 的影响。为了在模型中引入更多的生理学知识，仍有几个问题需要回答。为了解决这些问题，需要对人类污染病例和实验数据进行进一步的详细研究。该工作现在在欧洲辐射剂量学组 EURADOS 内继续进行。
