Chemical Sciences Division, Lawrence Berkeley National Laboratory , Berkeley, California , USA.
Int J Radiat Biol. 2014 Nov;90(11):1055-61. doi: 10.3109/09553002.2014.925150. Epub 2014 Aug 21.
To characterize the dose-dependent and sex-related efficacy of the hydroxypyridinonate decorporation agent 3,4,3-LI(1,2-HOPO) at enhancing plutonium elimination when post-exposure treatment is delayed.
Six parenteral dose levels of 3,4,3-LI(1,2-HOPO) from 1-300 μmol/kg were evaluated for decorporating plutonium in female and male Swiss-Webster mice administered a soluble citrate complex of (238)Pu and treated 24 hours later. Necropsies were scheduled at four time-points (2, 4, 8, and 15 days post-contamination) for the female groups and at three time-points (2, 4, and 8 days post-contamination) for the male groups.
Elimination enhancement was dose-dependent in the 1-100 μmol/kg dose range at all necropsy time-points, with some significant reductions in full body and tissue content for both female and male animals. The highest dose level resulted in slight toxicity, with a short recovery period, which delayed excretion of the radionuclide.
While differences were noted between the female and male cohorts in efficacy range and recovery times, all groups displayed sustained dose-dependent (238)Pu elimination enhancement after delayed parenteral treatment with 3,4,3-LI(1,2-HOPO), the actinide decorporation agent under development.
描述羟基亚乙基二膦酸酯解毒剂 3,4,3-LI(1,2-HOPO) 在延迟暴露后治疗时增强钚排出的剂量依赖性和性别相关疗效。
评估了雌性和雄性瑞士 Webster 小鼠在给予可溶性柠檬酸(238)Pu 复合物后 24 小时接受六种不同的 3,4,3-LI(1,2-HOPO) 给药剂量水平（1-300 μmol/kg），以确定其对钚的解毒作用。在雌性组的四个时间点（污染后 2、4、8 和 15 天）和雄性组的三个时间点（污染后 2、4 和 8 天）进行尸检。
在所有尸检时间点，1-100 μmol/kg 剂量范围内的消除增强呈剂量依赖性，所有雌性和雄性动物的全身体和组织含量均有明显降低。最高剂量水平导致轻微毒性，恢复期短，从而延迟了放射性核素的排泄。
虽然雌性和雄性队列在疗效范围和恢复时间方面存在差异，但所有组在延迟给予 3,4,3-LI(1,2-HOPO) 后均显示出持续的剂量依赖性（238）Pu 消除增强，3,4,3-LI(1,2-HOPO) 是正在开发的锕系元素解毒剂。
