Decorporation approach following rat lung contamination with a moderately soluble compound of plutonium using local and systemic Ca-DTPA combined chelation.
Decorporation efficacy of prompt pulmonary delivery of DTPA dry powder was assessed following lung contamination with plutonium nitrate and compared to an intravenous injection of DTPA solution and a combined administration of both DTPA compounds. In addition, efficacy of a delayed treatment was assessed. In case of either early or late administration, insufflated DTPA was more efficient than intravenously injected DTPA in reducing the plutonium lung burden due to its high local concentration. Prompt treatment with DTPA powder was also more effective in limiting extrapulmonary deposits by removing the early transportable fraction of plutonium from lungs prior its absorption into blood. Translocation of DTPA from lungs to blood may also contribute to the decrease in extrapulmonary retention, as shown by reduced liver deposit after delayed pulmonary administration of DTPA. Efficacy of DTPA dry powder was further increased by the combined intravenous administration of DTPA solution for reducing extrapulmonary deposits of plutonium and promoting its urinary excretion. According to our results, the most effective treatment protocol for plutonium decorporation was the early pulmonary delivery of DTPA powder supplemented by an intravenous injection of DTPA solution. Following inhalation of plutonium as nitrate chemical form, this combined chelation therapy should provide a more effective method of treatment than conventional intravenous injection alone. At later stages following lung contamination, pulmonary administration of DTPA should also be considered as the treatment of choice for decreasing the lung burden.
CEA/DSV/IRCM/Laboratoire de RadioToxicologie, Bruyéres-le-Châtel, 91297 Arpajor cedex - France. olivier.gremy@cea.fr
Olivier
O
Grémy
Nicolas
N
Tsapis
Sylvie
S
Bruel
Daniel
D
Renault
Anne
A
Van der Meeren
D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D009566:Nitrates / Q000737:chemistry* / Q000378:metabolism* / Q000652:urine; D004369:Pentetic Acid / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D011005:Plutonium / Q000737:chemistry* / Q000378:metabolism* / Q000652:urine; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012996:Solutions; D013997:Time Factors
D002614:Chelating Agents; D009566:Nitrates; D011208:Powders; D012996:Solutions; C015459:plutonium nitrate; D011005:Plutonium; D004369:Pentetic Acid