Removal of239Pu from mice with 3,4,3 LICAM(C) or N, N?, N?, N?-tetra-(2,3-dihydroxybenzoyl)-spermine

Abstract

Male mice SAS/4 were injected i.v. with 239Pu citr(IV) 0.27 microCi . kg-1-9.99 kBq X kg-1. After 1 h 30 mumol . kg-1 of 3,4,3 LICAM(C), N,N',N'',N'''-tetra-(2,3-dihydroxybenzoyl)-spermine or Na3CaDTPA as a reference compound was given intraperitoneally. After 4 days the animals were sacrificed and the Pu content in livers, kidneys, femurs and carcasses was determined by the liquid scintillation method. It was found that, as compared with the control, 3,4,3 LICAM(C) removed 83% of the Pu activity deposited in the liver, 71% of that in the femur and 79% of the Pu in the whole body. The Pu content in the kidneys exceeded the control value by about 50%. Na3CaDTPA removed 96, 86, 40 and 72% of plutonium from the liver, kidneys, femurs and carcasses respectively. Tetra-DHB-spermine caused the excretion of 50, 57 and 39% of Pu from liver, bone and whole body respectively. The retention of Pu in the kidneys was increased to 400% of the control value.

Rational Design of Sequestering Agents for Plutonium and Other Actinides

“…Reinvestigation in other laboratories of the efficacies of several siderophore-based ligands for decorporation of 238 Pu confirmed the initial assessments in mice of their effectiveness for in vivo and in vitro chelation of Pu(IV) relative to that of CaNa 3 -DTPA. 117,118,[171][172][173][174][175][176][177][178][179][180][181][182][183] These partnerships allowed for studies with other isotopes of Pu 180,[184][185][186][187][188] in addition to 238 Pu(IV) and other actinides, Am(III), 117,118,[171][172][173][174][175][176][177][178][179][180][181]184,187 Np(IV), 189 Np(V), [189][190][191] U(VI), 181,185,192 and Th(IV), 193 as well as actinides in chemical for...…”

“…Subsequent studies with the other animal models provided the opportunity to explore other methods of exposure to actinides, i.e., inhalation 117,[174][175][176]179,195,196,198 or wound contamination. [177][178][179][180]187,193,194 The collaborative projects also explored a variety of ligand administration regimens in addition to parenteral injection: 117,118,[172][173][174][175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191][193][194][195][196][197][198][199][200] local injection (either im or s.cut.) at a wound site, [177][178]…”

“…More importantly, the studies of other actinides and other exposure modes in several species revealed some ligand defects and some deleterious side effects that were not disclosed by the initial evaluation procedures in mice. [172][173][174][175][183][184][185]188,197,198,200 One important aspect of the new studies with alternative animal models is the opportunity to change the mode of administration of actinides, enabling simulation of various accident-based scenarios. Experiments to test the effects of chelating ligands on inhaled actinides involved the administration of a mixture of Pu and Am as a nitrate aerosol generated from nitric acid solutions through the use of a nebulizer over the period of 1 h. As one might imagine, the use of such a nebulizer on an animal as small as a mouse is very difficult; hence, 3-monthold female rats of the HMT strain, NRPB, weighing 180-200 g at the time of exposure, were used for studies determining the effects of inhaled actinides.…”

“…185 In a collaborative research program with the EU-LEP group, 3,4,3-LI-CAM(C) (53) was synthesized in several batches in their laboratories and designated EU-LI-CAM(C) (53). 175,183,315 The chelation of injected Pu citrate, inhaled Pu nitrate, and inhaled Pu-TBP was studied in several mouse and rat strains, Chinese and Syrian hamsters, and baboons. EU-LI-CAM(C) (53) was administered once (3-30 µmol kg -1 injected, 100 µmol kg -1 orally) or as many as five times in 4 days starting 30-60 min after iv injection of 238 Pu, and animals were killed at 1-28 days.…”

“…These renal Pu deposits, which were the greatest in Chinese hamsters and the least in mice, were cleared with a half-time of about 20 days. [172][173][174][175]183,188 Starting 30 min after rats inhaled an aerosol of 238 Pu nitrate, EU-LI-CAM(C) (53) or CaNa 3 -DTPA was injected once or five times in 4 days. Clearance of the Pu from lung and tissues by EU-LI-CAM(C) (53) was generally less than was obtained with CaNa 3 -DTPA; kidneys of rats given EU-LI-CAM(C) (53) contained Pu residues about as large as those observed in studies of injected Pu.…”