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 polyaminocarboxylic acid-based chelator, docosyl-triethylenetetraminepentaacetic acid (C22TT), was tested for its ability to promote decorporation of 239Pu and 241Am. The effects of dose and duration of treatment were determined in rats injected with 239Pu or 239Pu/241Am 2 weeks before the initiation of C22TT treatment and compared with untreated controls. In the dose-effects study, significant reductions in total body Am content were seen within 3 days after the initiation of C22TT treatment. After 30 days of treatment, there were dose-related reductions in the Pu and Am content of soft tissues and bones. All doses of C22TT resulted in substantial reductions in Pu and Am content of the liver. In the time-response study, there were rapid reductions in total body Am content in the C22TT-treated animals. The greatest reductions occurred within the first 30 days of treatment. Significant decreases in Pu content of soft and hard tissue were observed in the treated animals at 30, 60 or 90 days compared with untreated controls. The greatest reductions in organ Pu content occurred within the first 30 days of treatment, particularly in the liver, but it continued throughout the experiment. Neutron-induced autoradiography showed that C22TT greatly reduced the incorporation of Pu into new bone and substantially reduced the Pu content of the bone marrow. There was no evidence of overt toxicity in either experiment. This study demonstrates that orally administered C22TT is effective in reducing soft and hard tissue content of internally deposited Pu and Am.
Miller
S C
SC
Division of Radiobiology, School of Medicine, University of Utah, Salt Lake City.
Bruenger
F W
FW
Kuswik-Rabiega
G
G
Liu
G
G
Lloyd
R D
RD
D000085:Acetates / Q000008:administration & dosage*; D000284:Administration, Oral; D000576:Americium / Q000378:metabolism*; D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D008297:Male; D011005:Plutonium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014266:Trientine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000085:Acetates; D002614:Chelating Agents; C076893:docosyl-triethylenetetraminepentaacetic acid; D011005:Plutonium; D014266:Trientine; D000576:Americium