Efficacy of orally administered amphipathic polyaminocarboxylic acid chelators for the removal of plutonium and americium: comparison with injected Zn-DTPA in the rat.
Chelators are used to promote excretion of actinides and some other metals, but few are orally effective. The relative efficacies of orally administered triethylenetetraminepentaacetic acids (TT) with varying lipophilic properties on the removal of 241Am and 239Pu and comparison with parenteral Zn-DTPA was determined. The actinides were administered to adult rats 2 weeks prior to initiation of 30 d of chelation treatment. The TT compounds were given orally while Zn-DTPA was given twice weekly by injection. Total body content of 241Am was measured before and during the treatment period and organ contents of 241Am and 239Pu were measured at the end of the study. Significant reductions in 241Am occurred within the first week, with Zn-DTPA being the most effective. By 3 weeks, the most lipophilic chelator, C22TT was as effective as Zn-DTPA. After 30 d, reductions in organ content of 239Pu and 241Am directly correlated with increasing lipophilicity of the TT chelators. Oral C22TT was as effective as injected Zn-DTPA in liver and bone, the major organs of actinide deposition. The removal of 239Pu from the liver and reduction of redeposition of 239Pu in newly formed bone by C22TT was confirmed by neutron-induced autoradiographs. The amphipathic TT chelators may be useful as orally administered alternatives to current parenteral DTPA for the removal of actinide elements from the body, particularly for longer-term therapeutic applications.
Miller
Scott C
SC
Division of Radiobiology, Department of Radiology, University of Utah, 729 Arapeen Drive, Salt Lake City, Utah 84108, USA. Scott.Miller@hsc.utah.edu
Liu
Gang
G
Bruenger
Fred W
FW
Lloyd
Ray D
RD
D000085:Acetates / Q000008:administration & dosage* / Q000737:chemistry; D000284:Administration, Oral; D000576:Americium / Q000378:metabolism*; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002264:Carboxylic Acids / Q000008:administration & dosage*; D002614:Chelating Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism; D008297:Male; D004369:Pentetic Acid / Q000008:administration & dosage*; D011005:Plutonium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014266:Trientine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry
D000085:Acetates; D002264:Carboxylic Acids; D002614:Chelating Agents; C076893:docosyl-triethylenetetraminepentaacetic acid; D011005:Plutonium; D004369:Pentetic Acid; D014266:Trientine; D000576:Americium