Efficacy of 3,4,3-LIHOPO for Enhancing the Excretion of Plutonium from Rat after Simulated Wound Contamination as a Tributyl-n-phosphate Complex

Abstract

The siderophone analogue 3,4,3-LIHOPO, referred to hereafter as LIHOPO, has been examined for its ability to remove 238Pu in a tributyl-n-phosphate (TBP) complex from rat after intramuscular (i.m.) or subcutaneous (s.c.) contamination. The chelating agent was administered at a dosage of 30 mumol.kg-1, 30 min after the contamination, either by intravenous (i.v.) or local injection. By day 7 after exposure, local (i.m.) administration of LIHOPO reduced the amounts of i.m.-injected 238Pu in the would site, skeleton and liver to 75, 20 and 25% respectively of those in untreated animals. At the i.m. Pu would site, local treatment was superior to i.v. treatment; both ligands were equally effective. At the s.c. Pu would site, local and systemic treatments were equally effective and LIHOPO was superior to DTPA. After translocation, LIHOPO was the most effective treatment for enhancing Pu excretion, whatever the route of contamination and treatment: the administration of LIHOPO and DTPA reduced whole-body Pu retention by a factor of 1.8 and 1.4 respectively. All these results are encouraging for the use of LIHOPO in the future but more studies are needed, concerning both the toxicity of the compound and its use in man.

Efficacies of Three Chelating Agents on Removal of Plutonium in Rats: Comparison of CBMIDA, 3,4,3-LIHOPO and Ca-DTPA

“…These results supported the finding that the removal effect of 3, 4, 3-LIHOPO is superior to that of Ca-DTPA. 16,17,26) The effects of the 3, 4, 3-LIHOPO in this study was greater than those previous studies,17,24,25) probably due to the different administration routes of plutonium, e. g., inhalation and subcutaneous muscles. As well the timing of the administration of chelating agents after plutonium administration, because the effects of chelating agents depends on the plutonium concentration in the blood and the clearance time of the chelating agent.…”

“…However, as the effect of a single administration of Ca-DTPA for removing plutonium is low,14) a long term chelation therapy may be necessary. 15) After DTPA, as an agent superior to Ca-DTPA, linear tetrahydroxypydinone (3,4, in Western countries, [16][17][18][19][20][21][22][23][24][25][26] and Catechol-3, 6-bis (methyleiminodiaetic acid) (CBMIDA) and their analogues in Japan and China27,28) have been developed. Comparisons of CBMIDA and Ca-DTPA,27) and Zn-DTPA,27,28) and of 3, 4, 3-LIHOPO and Ca-DTPA17, 18,22,[24][25][26] in regard to their removal of plutonium have been performed.…”

Importance of Charge Transfer and Polarization Effects for the Modeling of Uranyl−Cation Complexes

“…A major rationale for much actinide work has been that of detoxification after contamination due to accident or dumping. Thus, effort has gone into the identification of agents that promote the excretion of uranium, 4 plutonium, 5 and neptunium 6 from the human body and into how to separate actinide ions from other ions in the management of nuclear waste. 7,8 Molecular modeling and theoretical simulation studies are potentially powerful approaches for tackling such problems and can be used, for example, to compute the association constant of different chelating agents to uranium or plutonium in solution.…”

“…A major rationale for much actinide work has been that of detoxification after contamination due to accident or dumping. Thus, effort has gone into the identification of agents that promote the excretion of uranium, plutonium, and neptunium from the human body and into how to separate actinide ions from other ions in the management of nuclear waste. , …”

Chelation of Actinides

“…19,32,52 after extensive toxicity and efficacy studies in mice and a limited number of tests in dogs and baboons, two particular molecules, 3,4,3-lI(1,2-hOpO) 8 and 5-lIO(Me-3,2-hOpO) 9, were selected as promising orally available candidate actinide decorporation agents. [53][54][55][56][57][58][59][60][61][62][63][64][65][66] both compounds were found to be 30 times more potent than Dtpa for the decorporation of pu(iv), and to sequester a wider spectrum of radionuclides, including U and Np, as well as particulate contaminants from mixed oxide fuel. 52,67 In addition, unlike Dtpa, both molecules have the advantage of being efficacious in the oral delivery format.…”