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

The effectiveness of the siderophore analogues DFO-HOPO (a hydroxypyri done derivative of desferrioxamine) and 3,4,3-LIHOPO (a linear tetrahy droxypyridinone) for the decorporation of Pu-238 and Am-241 from rat w as studied. (1) Dosage-effect relationship. A similar treatment effect on Pu was achieved by single s.c. injection of 30 mu mol kg(-1) or by oral administration of 100 mu mol 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 bon es was reduced by LIHOPO to <10% of control values. No increase in ren al retention of the actinides was observed. Whilst DFO-HOPO did not af fect Am retention, a substantial reduction was achieved by LIHOPO. Rem oval effectiveness for injected LIHOPO on Pu was higher than that on A m, especially in the bones and after low ligand doses. Orally administ ered small doses of LIHOPO, however, mobilized more Am than Pu, both f rom the liver and the bone. (2) Time-effect relationship. The effectiv eness of the injected ligands for Pu decreased exponentially with the time between exposure and treatment. With DFO-HOPO, the calculated hal f-times for decrease of mobilized fractions of Pu from the bone and li ver were 5 and 12 h respectively. The effect of LIHOPO on Pu decreased much more slowly, with a halftime of 3-4 weeks. For instance, a singl e injection of 30 mu mol kg(-1) LIHOPO at 10 days post-Pu removed 30 a nd 50% activity from the bone and liver respectively. The removal effe ct of LIHOPO for Am in the liver decreased with time in the same way a s for Pu but the mobilized fractions of skeletal and renal Am decrease d from the first day with a half-time of only 8 and 4 days respectivel y.