Mobilization and detoxification of polonium-210 in rats by 2,3-dimercaptosuccinic acid and its derivatives

Purpose: To reduce retention and toxicity of the alpha particle emitter pol onium-210 in rats by newly developed chelating agents. Materials and methods: Repeated subcutaneous chelation was conducted after intravenous injection of Po-210 nitrate. For reduction of Po-210 retention the treatment with vicinal dithiols meso-and rac-2,3-dimercaptosuccinic aci d (DMSA), mono-i-amy-lmeso-2,3-dimercapto succinate (Mi-ADMS) and mono-N-(i -butyl)-meso-2,3-dimercapto succinamide (Mi-BDMA) were used. For the reduct ion of toxic effects of Po-210, treatment effectiveness of Mi-BDMA was comp ared with that of N,N'-di(2-hydroxyethyl)ethylenediamine-N,N'-biscarbodithi oate (HO-EtTTC, reference compound). Results: Treatment with meso-DMSA and rac-DMSA altered the main excretion r oute of Po-210, reduced its contents in the liver but increased its deposit ion in the kidneys. Treatment with Mi-ADMS or Mi-BDMA increased total excre tion of (210)po, mainly via the faeces. Only Mi-BDMA decreased Po-210 level s in the kidneys. The effectiveness of all chelators decreased with delay i n the start of treatment. In a survival study, the lives of rats treated ea rly with Mi-BDMA or delayed with HOEtTTC were prolonged three-fold when com pared with rats receiving a lethal amount of Po-210 only. Conclusions: Of the vicinal dithiols examined, Mi-BDMA was the best mobiliz ing chelating agent for Po-210 and it reduced Po-210 toxicity when the trea ment started immediately. However, the detoxification efficacy of the immed iate treatment with HOEtTTC, observed in our previous study, was superior t o that of the present result with Mi-BDMA.