Decorporating efficacy of catecholaminocarboxylate chelating agents for thorium-234 and protective effects on associated radiation injury

Abstract

The aim was to identify the decorporation and anti-oxidation efficacy of prompt and delayed consecutive administration of the catecholicpolyaminopolycarboxylate ligands 9501 and 7601 for radiothorium in vivo. The chelating agents 9501 or 7601 were administered intramuscularly to ICR mice 3 min or 3 days after intraperitoneal injection of 30 MBq kg – 1 234Th-citrate for 3 consecutive days. The animals were killed 4 or 5 days after administration of the chelating agents, respectively. The 234Th radioactivity in the whole-body and its retention in liver and skeleton were determined. Malondialdehyde (MDA) production, as an index of 234Th-induced lipid peroxidation in bone marrow and liver, was assayed and the number of bone marrow nucleated cells (NBMNC) were counted. The pathological changes of bone marrow and liver tissue were observed. CaNa3-diethylenetriaminepentaacetate (DTPA) and vitamin E were used as controls. The competitive ability of 9501 and 7601 to mobilize thorium with bovine serum albumin (BSA) was studied. Their inhibitory effect on superoxide anion radicals was measured by electron spin resonance. When promptly injected, 9501 or 7601 were superior to CaNa3-DTPA for reducing 234Th retention in mouse. Their different bioactivity for decorporation of 234Th was consistent with their competitive ability to mobilize thorium with BSA. Although the removal effectiveness of 9501 and 7601, given by delayed injection, was lower than that of the prompt administration, they could inhibit 234Th-induced lipid peroxidation. This caused significant reductions of MDA content in bone marrow and liver and markedly ameliorated histological changes to bone marrow and liver tissue in 234Th-treated mice. Their protective effects were better than CaNa3-DTPA and vitamin E. 9501 and 7601 could directly scavenge . Their effects as scavengers were very significant. The chelating agents 9501 and 7601 are able to remove thorium as effectively as other commonly used agents like CaNa3-DTPA and reduce radiation dose. In addition, these agents have anti-oxidative action reducing both cell killing in the bone marrow and malondialdehyde levels, a measure of lipid peroxidation, in the bone marrow and liver. The protection from internally deposited radioactive material was predictable by the chelators' competitive ability to chelate thorium from BSA and their ability to act as an oxygen free-radical scavenger. The duel effect of reducing radiation dose and response could be important in reducing the risk from internally deposited gamma radionuclides.