Forty-eight adult beagles were injected with 0.00179 to 4.49 pCi 241Am/kg body mass. Retained activity in the living animals was evaluated via the 60 keV gamma-ray using a combination of total-body and partial-body counting to determine the proportion in the liver and in non-liver tissue. Soon after injection, about 50% and 40%, respectively, of the administered 241Am was deposited in the liver and non-liver tissue (mainly skeleton). In the animals injected with 0.00179-0.305 pCi/kg the liver and non-liver burdens decreased slowly each with a biological half-time of about 10 yr during the first 850 days. Two dogs injected with about 2.80 ,uCi/kg exhibited a sharp decrease in liver retention beginning about 100 days after injection accompanied by an increase in non-liver 241Am. Both showed extreme degenerative liver changes at death 401 and 448 days after injection. Similar but more slowly progressing effects were observed in the retention of 241Am by two animals injected with about 0.904pCi/kg. Excreta collections from four dogs during the first 3 weeks after injection showed that f of the excretion was urinary and that nearly 2 of the total z41Am excreted during this period appeared in the first day's collection. Evaluation of the activity of individual bones, organs, and tissues of six animals autopsied 1-448 days after injection showed that although 241Am was distributed in many soft tissues, the liver and skeleton were the principal deposition sites; however, americium concentration in the thyroid gland was higher than in the skeleton and was higher than in any other soft tissue except the liver. Autoradiography showed that 2aArn was deposited close to the location of the functioning thyroid cells. The kidney also had a relatively high concentration of activity, selectively deposited in the glomeruli.
Fourteen young adult beagles were injected with 0.9 pCi/kg of polymeric 239Pu to which tracer amounts of gamma-ray emitting O'Pu had been added at the final stage of the polymerization process. Beginning 2 hr after Pu administration, four of the dogs were given injections of 30pmole/kg Zn-DTPA once each day, and four dogs were given injections of 30 pmole/kg Ca-DTPA once each week. These dosages and frequencies have been suggested for use in humans and are safe for adult beagles. Total ='Pu excretion in the first 24 hr averaged 14.6k 5.2% (S.D.) with Ca-DTPA, 10.42 2.1% with Zn-DTPA and 7.1 2 1.2% with no DTPA, while corresponding averages for the first 28 days cumulative excretion, corrected for radioactive decay, were 38.2% (Ca-DTPA), 49.4% (Zn-DTPA) and 12.1% (no DTPA). Although the daily 237Pu excretion by the Ca-DTPA dogs between DTPA injections continued to be greater than that of the untreated animals, substantially better decorporation was achieved by the more frequent administration of Zn-DTPA. In vivo counting showed that, in the untreated dogs, non-liver 237Pu increased as a function of time, indicating that some 237Pu was translocated from the liver to the non-liver tissue (mainly skeleton) with increasing time (2% retention at 1 day, 35% at 6 weeks and 38% at 23 weeks after injection), while liver content decreased from 64 to 53 to 48% at corresponding times. These findings were verified by tissue distribution studies in 2 dogs sacrificed at 33 and 40 days. However, biological retention of 237Pu within non-liver tissue remained nearly constant (-23%) in the Ca-DTPA dogs for the first 6 weeks of treatment while 237Pu in the liver was reduced from about 60 to 34%. In contrast, activity was lost by animals given Zn-DTPA from both liver and non-liver tissue during the same period of time, declining from about 60 to 25% and 28 to 17%, respectively. Between 6 and 23 weeks of therapy, 23'Pu in liver and in non-liver tissue decreased in the Ca-DTPA animals to 23 and 16%. respectively, while retention in the Zn-DTPA dogs was reduced to 13 and 10%. The excretion and distribution studies suggest that some of the '"PU was metabolized in a fashion similar to that of monomeric Pu and some as polymeric Pu, simulating a mixture of "soluble" and "insoluble" plutonium as might be encountered in a typical accident. We conclude that daily injections of Zn-DTPA are more effective in the removal of incorporated plutonium than are weekly injections of Ca-DTPA.
The risk of americium-induced liver cancer in beagle dogs that received long-term dietary ethanol was two to three times that of their nonalcoholic cohorts, even though the radionuclide retention time in hepatic tissue was shortened by the alcohol treatment. Liver malignancies did not occur in the ethanol-treated, nonirradiated controls. An ethanol-induced tumor-promoting effect was not observed in organs or tissues other than the liver.
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