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The body content of certain radionuclides and the consequences of accidental incorporation may be reduced by treatment with chelating agents. Such agents have been widely studied and have proved to be useful in man. Chelation therapy may also be advantageous in certain cases of heavy metal poisoning. There is still a need to develop new, more efficient and less toxic agents and better therapeutic schedules for using the existing agents. So far as possible the testing of potential new compounds should be carried out using standardized methods. [ABSTRACT FROM AUTHOR]

Male SAS/4 mice were injected i.v. with 6.6 kBq 239Pu-citrate. After 1 or 24 h a single i.p. injection of 15 or 30 mumol kg-1 or repeated (three or four) daily injections of 30 mumol kg-1 of tetra-THB-spermine were given, and at 4 or 7 days Pu retention was measured in liver, kidneys and femur. Besides tetra-THB-spermine, equimolar doses of tetra-DHB-spermine were injected for comparison, or equimolar doses of diethylene triamine-pentaacetic acid (DTPA) as a reference compound. Histological changes in kidneys and liver were examined after i.p. injections of 30 mumol kg-1 or at 2-13 times higher doses of tetra-THB-spermine. The results show that: (1) Introduction of an additional hydroxy group into the aromatic moieties of tetra-DHB-spermine results in increased hydrophilicity, lower toxicity and a lower renal retention of Pu. (2) Tetra-THB-spermine and tetra-DHB-spermine are similarly effective in removing plutonium from liver and bone. Their efficacies in removing Pu from bone are approximately similar to those of DTPA but for whole-body removal they are generally inferior. (3) Multiple (30 mumol kg-1) of tetra-THB-spermine were no more effective than a single injection at mobilizing Pu from the liver. (4) Four injections of tetra-THB-spermine induced cloudy swelling and fatty degeneration in epithelial cells of the proximal convoluted tubules. At levels of 400 mumol kg-1 tetra-THB-spermine produced severe degenerative glomerular lesions, foci of liver necrosis and thromboses of the portal vein branch.

65Zn, 60Co or 144Ce was injected intravenously into rats at various stages of pregnancy. Six hours later, DTPA chelate of non-radioactive Ca, Zn or Co was given intraperitoneally. Another group of pregnant rats received intravenous injection of 65ZnDTPA or 60CoDTPA. In both experiments, 24 hours after administration, the concentration of the radioactive material was determined in the dam's whole body as well as in foetuses, chorioallantoic placentae and yolk sacs. 65Zn and 60Co, which had been administered to the rats as DTPA complexes, were found not to pass from the dam's blood to the foetuses or to pass only in very minute amounts. This finding could be considered as an indirect indication that DTPA chelates do not penetrate the placental barrier. Nevertheless, the chelates injected intravenously into the dam early after an internal contamination, decrease the radionuclide content in the foetuses. No substantial effects of pregnancy on the effectiveness of the chelate in removing radionuclides from the body of rats were observed.

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.