PURPOSE: This manuscript compares the behavior of monomeric (239)Pu(4+)-citrate injected intravenously in rats and dogs with a comparison of available humans' data. MATERIAL AND METHODS: The experimental design for these two studies consisted of eight groups sacrificed at predetermined time-points post exposure. All organs and tissues as well as daily urinary and fecal excretion were analyzed. RESULTS: Liver and skeleton were the organs with the highest (239)Pu uptake in both species; 76% in dogs and 70% in rats at 24 hours (h) post IV administration. By the end of the study (28 days, d), the activity in skeleton and liver was 85% in dogs and 65% in rats. The urinary excretion function seems to be similar for rats, dogs and humans but the daily fecal to urinary excretion ratio differs between species. CONCLUSION: A rapid clearance from the liver of rats was observed compared to dogs. Skeleton-to-liver ratios are variable between species. Urinary and fecal excretion patterns for dogs are consistent with human data, indicating that dogs seem to represent better the (239)Pu behavior in humans. The data confirm that the better animal model to evaluate the efficacy of (239)Pu chelating compounds is the canine model.
PURPOSE: This manuscript compares the behavior of monomeric (239)Pu(4+)-citrate injected intravenously in rats and dogs with a comparison of available humans' data. MATERIAL AND METHODS: The experimental design for these two studies consisted of eight groups sacrificed at predetermined time-points post exposure. All organs and tissues as well as daily urinary and fecal excretion were analyzed. RESULTS: Liver and skeleton were the organs with the highest (239)Pu uptake in both species; 76% in dogs and 70% in rats at 24 hours (h) post IV administration. By the end of the study (28 days, d), the activity in skeleton and liver was 85% in dogs and 65% in rats. The urinary excretion function seems to be similar for rats, dogs and humans but the daily fecal to urinary excretion ratio differs between species. CONCLUSION: A rapid clearance from the liver of rats was observed compared to dogs. Skeleton-to-liver ratios are variable between species. Urinary and fecal excretion patterns for dogs are consistent with human data, indicating that dogs seem to represent better the (239)Pu behavior in humans. The data confirm that the better animal model to evaluate the efficacy of (239)Pu chelating compounds is the canine model.
Authors: Benjamin E Allred; Peter B Rupert; Stacey S Gauny; Dahlia D An; Corie Y Ralston; Manuel Sturzbecher-Hoehne; Roland K Strong; Rebecca J Abergel Journal: Proc Natl Acad Sci U S A Date: 2015-08-03 Impact factor: 11.205