Bis-dithiocarbamates: Effective Chelating Agents for Mobilization of Polonium-210 from Rat

Abstract

The time dependence of organ distribution and excretion of intravenously (iv) injected ²¹⁰Po was investigated after the single or repeated administration of NN′-diethylamine-N-carbodithioate (diethyldithiocarbamate, DDTC) and three bis-dithiocarbamates: NN′-dimethylethylenediamine-NN′-biscarbodithioate (MeTTC), NN′-diethylethylenediamine-NN′-biscarbodithioate (EtTTC), and N'N′-di(2-hydroxyethyl)ethylene-diamine-NN′-biscarbodithioate (HOEtTTC). The biokinetics of iv injected ²¹⁰Po was used as a model for the behaviour of ²¹⁰Po absorbed into the blood from any other site of entry into the body. The most effective chelating agent was HOEtTTC, which was not only effective when injected subcutaneously (sc) immediately after ²¹⁰Po, but also 1 h later. Toxic effects of DDTC were observed in a metabolic study when the effect of HOEtTTC was compared with that of DDTC. DDTC caused accumulation of ²¹⁰Po in brain and transiently in liver. When HOEtTTC was administered, the faecal excretion of ²¹⁰Po was increased from the very beginning. MeTTC, EtTTC and N-(2,3-dimercaptopropyl)phtalamidic acid (DMPA) were ineffective when the treatment started 1 h after iv injection of ²¹⁰Po.