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La Recherchev2

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Efficacy of 3,4,3-Li(1,2-HOPO) for décorporation of MOX compound in rat and monkey after intramuscular injection.


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Workshop on Internal Dosimetry of Radionuclides - Occupational, Public and Medical Exposure - 9-12 September 2002 - New College, Oxford, United Kingdom
F. PAQUET1, V. CHAZEL1, M. DONNADIEU-CLARAZ1, P. HOUPERT1, R. GUILMETTE2 ; B. MUGGENBURG2, NIKULA,K2.

Résumé

3,4,3-LI(1,2-HOPO), designed hereafter as Lihopo, is known to be the most effective siderophore analogue yet tested for the decorporation of actinides. However, its efficacy for uranium or plutonium decorporation after administration as mixed compound remains unknown. This study aimed at assessing the efficiency of Lihopo for reducing uranium, plutonium and americium in rats and monkeys after intramuscular injection of MOX (mixed oxides) compound.

Sixteen F344/Crl female rats and six adult female cynomolgus monkeys were contaminated by intramuscular injection of a saline solution containing a suspension of 1mg MOX. Immediately after injection, animals were housed in metabolic cages for separate collection of urine and feces. Three groups of 4 rats were treated with chelating agents (Lihopo 30 µmol.kg-1; Lihopo 200 µmol.kg-1; DTPA 30 µmol.kg-1) whereas one group of 3 monkeys was treated with Lihopo 30 µmol.kg-1. Control rats and monkeys were treated with NaCl 0.9%. The chelating agents were injected intramuscularly exactly at the same site as the MOX contamination, 30 min, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d and 7 d after exposure and the animals were sacrificed 24h after the last treatment. In addition to the biokinetic studies, histopathological and toxicological studies were performed on the monkeys to assess the Lihopo toxicity.

The results showed that 85% of the deposited U was translocated from the wound site 8 d after contamination, whereas translocation of Am and Pu varied from 5 to 50% of the initial wound deposit.
Lihopo reduced Pu and Am retention in carcass (muscles and skeleton) by a factor 2 and increased urinary plus faecal excretion by a factor 20. By contrast, Lihopo had no effect on the urinary excretion of uranium and had little effect on its faecal excretion (factor 1.3). Uranium retention in the carcass was reduced by a factor 2 in carcass but was increased by the same factor in kidneys. Histopathology performed on monkeys showed a mild inflammation and necrosis localized to the injection site, compatible with an increase of lactate dehydrogenase. Two of monkeys that received MOX and Lihopo had renal lesions, tubulointerstitial nephritis or glomerulonephritis. All three monkeys that received lihopo had hepatic lesions.
As a conclusion, it appears that Lihopo was efficient to remove Pu and Am from the wound site but not uranium. Moreover Lihopo showed some toxicity after intramuscular injection that should be investigated before any recommendation for human use.

 

1. Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection de la santé de l’Homme et de Dosimétrie, Service de Dosimétrie, Laboratoire d’Etudes Appliquées de Radiotoxicologie, BP 36, F-26701 Pierrelatte Cedex, France
2. Lovelace Respiratory Research Institute, P.O. Box 5890, Albuquerque, New Mexico 87185 USA.