Decorporation from Beagles of a Mixture of Monomeric and Particulate Plutonium Using Ca-DTPA and Zn-DTPA

Abstract

Fourteen young adult beagles were injected with 0.9 μCi/kg of polymeric 239Pu to which tracer amounts of gamma-ray emitting 239Pu 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 30 μmole/kg Zn-DTPA once each day, and four dogs were given injections of 30 μmole/kg Ca-DTPA once each week. These dosages and frequencies have been suggested for use in humans and are safe for adult beagles. Total 237Pu excretion in the first 24 hr averaged 14.6 ± 5.2% (S.D.) with Ca-DTPA, 10.4 ± 2.1% with Zn-DTPA and 7.1 ± 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 (29% 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 (about 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, 237Pu 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 237Pu 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.