Stradling G N, Gray S A, Moody J C, Hodgson A, Raymond K N, Durbin P W, Rodgers S J, White D L, Turowski P N
National Radiological Protection Board, Didcot, Oxon, UK.
Int J Radiat Biol. 1991 May;59(5):1269-77. doi: 10.1080/09553009114551131.
A hydroxypridinone derivative of desferrioxamine (Na-DFO-HOPO), a dihydroxamic derivative of diethylenetriaminepenta-acetic acid (ZnNa-DTPA-DX), and DTPA (CaNa3- and ZnNa3-DTPA) were tested at dosages of 30 mumol kg-1 for their ability to remove 238Pu or 241Am from rats after their intravenous injection as citrate or inhalation as nitrate. The most effective treatment regimen for injected Pu was the repeated administration of DFO-HOPO; by 7 days the body content was reduced to 8% of that in untreated animals. Repeated dosages of 3 mumol kg-1 DFO-HOPO were as effective as those of 30 mumol kg-1 DTPA. After inhalation of Pu nitrate, repeated treatment with DTPA, DTPA-DX or DFO-HOPO reduced the body content by 7 days to, respectively, 10, 15 and 31% of those in untreated animals. After inhalation of Am, DTPA-DX and DTPA were equally effective, the body contents being reduced to 7% of control values with repeated treatment. Injection of DFO-HOPO was ineffective for enhancing the elimination of inhaled or injected Am. The results confirm the strategy of examining the use of siderophore analogues for the decorporation of Pu or Am. However, at present DTPA should remain the agent of choice, particularly after inhalation.
去铁胺的一种羟基吡啶酮衍生物(Na-DFO-HOPO)、二乙烯三胺五乙酸的一种二异羟肟酸衍生物(ZnNa-DTPA-DX)以及二乙三胺五乙酸(CaNa3-DTPA和ZnNa3-DTPA),以30 μmol/kg的剂量进行测试,观察它们在静脉注射柠檬酸盐形式的238Pu或241Am后,以及吸入硝酸盐形式的238Pu或241Am后,从大鼠体内清除这些物质的能力。对于注射的钚,最有效的治疗方案是重复给予DFO-HOPO;到第7天时,体内含量降至未治疗动物的8%。3 μmol/kg的DFO-HOPO重复给药与30 μmol/kg的二乙三胺五乙酸效果相同。吸入硝酸钚后,用二乙三胺五乙酸、二乙三胺五乙酸 - DX或DFO-HOPO重复治疗,到第7天时,体内含量分别降至未治疗动物的10%、15%和31%。吸入镅后,二乙三胺五乙酸 - DX和二乙三胺五乙酸效果相同,重复治疗后体内含量降至对照值的7%。注射DFO-HOPO对增强吸入或注射镅的清除无效。结果证实了研究使用铁载体类似物促进钚或镅排出体外的策略。然而,目前二乙三胺五乙酸仍应是首选药物,尤其是在吸入后。