Removal of Pu and Am from Beagles and Mice by 3,4,3-LICAM(C) or 3,4,3-LICAM(S)

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Abstract
Decorporation of Pu and Am by tetrameric catechoylamide (CAM) ligands was investigated in beagles and mice. Eight dogs were injected (i.v.) with 237 + 239Pu(IV) + 241AM(III) citrate, and 30 min later, pairs of dogs were injected i.v. with 30 .mu.mol/kg of 3,4,3-LICAM(C) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-5-sulfobenzoyl)tetraazatetradecane, tetrasodium salt], 3,4,3-LICAM(S)[N1,N5,N10,N14-tetrakis(2,3-dihydroxy-4-carboxybenzoyl)tetraazatetradecane, tetrasodium salt], CaNa3-DTPA [CaNa3-diethylenetrianine pentaacetic acid], or each of the latter 2 ligands. Blood was sampled, and excreta were collected for 7 days; at that time, the dogs were sacrificed, and nuclide retention in liver and nonliver tissue was measured. Groups of 5 mice were each given 238Pu(IV) or 241Am(III) citrate i.v.; 3 min later, 30 .mu.mol/kg of a CAM ligand was injected i.p.; mice were killed at 24 h, and separated excreta and tissues were analyzed. In the dogs, average retention at 7 days of the injected Pu and Am, respectively, was as follows: 12 and 70% after treatment with a CAM ligand alone; 30 and 20% after DTPA; 12 and 20% after LICAM(S) plus DTPA; 90 and 89% without a ligand. In the mice, mean retention of the injected Pu and Am, respectively, was as follows: 14 and 66% after treatment with LICAM(C); 21 and 54% after LICAM(S); 91 and 87% without a ligand. In both species, about 99% of net Pu excretion (excretion with ligand - excretion without ligand) promoted in 24 hr by DTPA or LICAM(S) was in the urine, whereas about 10% of net Pu excretion promoted by the less hydrophilic LICAM(C) was in feces. Delayed excretion of both Am and Pu was significant in all ligand-treated dogs. Comparison of the nuclide content of tissues of ligand-treated mice with those of mice killed 3 min after nuclide injection indicated that the CAM ligands chelated circulating Pu and Am and prevented further deposition. In addition, the CAM ligands removed much of the presumably loosely bound Pu present in liver and skeleton at the time of ligand injection. LICAM(C) was more effective in removing Pu from liver, and LICAM(S) was more effective in the skeleton. Moderate to severe uremia and histological evidence of cell killing in the distal tubules of the kidney were observed in the 4 dogs injected once with 30 .mu.mol/kg of LICAM(S). However, blood urea nitrogen levels were normal, and no lesions were found in any tissue of 2 dogs given 1 injection or mice given 20 injections of 30 .mu.mol/kg of LICAM(C). LICAM(C) is less acidic than LICAM(S), which reduces its ability to chelate Fe(III) at the pH of tubular urine, and its lesser hydrophilicity allows diversion of some ligand to the GI tract and away from the kidneys.