Relative efficacy of potassium iodide and ammonium perchlorate as antidotes to radioiodide exposure in the adult rat and its implications on disaster preparedness

Abstract

In consideration of the therapeutic efficacy of pharmaceutical intervention for blocking uptake of radioiodide (131I-) into the thyroid gland from nuclear fallout or terrorist attack, there is a paucity of data for treatment post 131I- contamination for differing pharmaceutical approaches to the treatment of 131I- poisoning. Currently the only method of treating 131I- exposure that is approved by the Food and Drug Administration is potassium iodide (KI), and though effective, it has significant limitations, as evidence by over 10,000 thyroid cancers following KI treatment of Chernobyl victims. Experiments were conducted to compare KI to perchlorate (ClO4-), a known iodide uptake inhibitor with a higher affinity for the sodium-iodide symporter and thyroid receptor sites, to determine if advantages could be manifested by perchlorate administration rather than KI for 131I- poisoning. In initial experiments, it was determined that both KI and perchlorate dosed rats had a relatively equal efficiency in blocking the uptake of 131I- into the thyroid when administered following the 131I- dose. However, when serum and urine endpoints were considered, we discovered that animals dosed with perchlorate contained markedly lower serum concentrations of 131I- and markedly increased cumulative urine amounts of 131I-. Following these results the focus was primarily on urinary excretion as the underlying determinant of which prophylactic approach was more beneficial. Urine time-course data revealed that over three days of urine collection no significance between cumulative urinary 131I- excretions existed between KI and perchlorate dosed animals. However, during the first day of collection it was determined that animals on perchlorate treatment excreted 131I- more than did animals administered KI. Thyroidal 131I- discrepancies were noted with significantly reduced concentrations of 131I- in animals administered KI. Thyroxine was then administered in conjunction with KI and perchlorate therapy with similar urinary excretion profiles and no significance in thyroidal concentrations of 131I-. We concluded from the current work that perchlorate has an equivalent efficacy in blocking uptake of thyroidal 131I- accumulation, while excreting 131I- with a higher intensity than KI. It is therefore our recommendation that perchlorate be more thoroughly investigated as a pharmaceutical intervention for acute 131I- poisoning.