title: Chelation therapy by DFO-HOPO and 3,4,3-LIHOPO for injected Pu-238 and Am-241 in the rat: effect of dosage, time and mode of chelate administration.
abstract: The effectiveness of the siderophore analogues DFO-HOPO (a hydroxypyridone derivative of desferrioxamine) and 3,4,3-LIHOPO (a linear tetrahydroxypyridinone) for the decorporation of 238Pu and 241Am from rat was studied. (1) Dosage-effect relationship. A similar treatment effect on Pu was achieved by single s.c. injection of 30 mumol kg-1 or by oral administration of 100 mumol kg-1 of either of the two ligands, provided the oral dose was administered earlier. In general, LIHOPO was more effective than DFO-HOPO: retention of Pu in the liver and bones was reduced by LIHOPO to < 10% of control values. No increase in renal retention of the actinides was observed. Whilst DFO-HOPO did not affect Am retention, a substantial reduction was achieved by LIHOPO. Removal effectiveness for injected LIHOPO on Pu was higher than that on Am, especially in the bones and after low ligand doses. Orally administered small doses of LIHOPO, however, mobilized more Am than Pu, both from the liver and the bone. (2) Time-effect relationship. The effectiveness of the injected ligands for Pu decreased exponentially with the time between exposure and treatment. With DFO-HOPO, the calculated half-times for decrease of mobilized fractions of Pu from the bone and liver were 5 and 12 h respectively. The effect of LIHOPO on Pu decreased much more slowly, with a half-time of 3-4 weeks. For instance, a single injection of 30 mumol kg-1 LIHOPO at 10 days post-Pu removed 30 and 50% activity from the bone and liver respectively. The removal effect of LIHOPO for Am in the liver decreased with time in the same way as for Pu but the mobilized fractions of skeletal and renal Am decreased from the first day with a half-time of only 8 and 4 days respectively.
authors.affiliation: National Institute of Public Health, Centre of Industrial Hygiene and Occupational Diseases, Praha, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Volf
authors.forename: R
authors.initials: R
authors.lastname: Burgada
authors.forename: K N
authors.initials: KN
authors.lastname: Raymond
authors.forename: P W
authors.initials: PW
authors.lastname: Durbin
mesh_terms: D000576:Americium; D000818:Animals; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology*; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003676:Deferoxamine / Q000031:analogs & derivatives*; D005260:Female; D011005:Plutonium; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002396:Catechols; D002614:Chelating Agents; D011728:Pyridones; D011868:Radioisotopes; C080802:1,5,14-tris(2,3-dihydroxybenzoyl)-10-(1-hydroxy-2-pyridon-6-oyl)-1,5,10,14-tetraazatetradecane; D011005:Plutonium; D003676:Deferoxamine; D000576:Americium