DURATION AND DOSE-RELATED EFFECTS OF AN ORALLY-ADMINISTERED, PARTIALLY LIPOPHILIC POLYAMINOCARBOXYLIC ACID ON THE DECORPORATION OF PLUTONIUM AND AMERICIUM

A recently developed, orally administered, partially lipophilic polyam inocarboxylic acid-based chelator, docosyl-triethylenetetraminepentaac etic acid (C22TT), was tested for its ability to promote decorporation of Pu-239 and Am-241. The effects of dose and duration of treatment w ere determined in rats injected with Pu-239 or Pu-239/Am-241 2 weeks b efore the initiation of C22TT treatment and compared with untreated co ntrols. In the dose-effects study, significant reductions in total bod y Am content were seen within 3 days after the initiation of C22TT tre atment. After 30 days of treatment, there were dose-related reductions in the Pu and Am content of soft tissues and bones. All doses Of C22T T resulted in substantial reductions in Pu and Am content of the liver . In the time-response study, there were rapid reductions in total bod y Am content in the C22TT-treated animals. The greatest reductions occ urred within the first 30 days of treatment. Significant decreases in Pu content of soft and hard tissue were observed in the treated animal s at 30, 60 or 90 days compared with untreated controls. The greatest reductions in organ Pu content occurred within the first 30 days of tr eatment, particularly in the liver, but it continued throughout the ex periment. Neutron-induced autoradiography showed that C22TT greatly re duced the incorporation of Pu into new bone and substantially reduced the Pu content of the bone marrow. There was no evidence of overt toxi city in either experiment. This study demonstrates that orally adminis tered C22TT is effective in reducing soft and hard tissue content of i nternally deposited Pu and Am.