Evaluation of Potassium Iodide (KI) and Ammonium Perchlorate (NH ₄ ClO ₄ ) to Ameliorate ¹³¹ I ^- Exposure in the Rat

Abstract

Nuclear reactor accidents and the threat of nuclear terrorism have heightened the concern for adverse health risks associated with radiation poisoning. Potassium iodide (KI) is the only pharmaceutical intervention that is currently approved by the Food and Drug Administration for treating (131)I(-) exposure, a common radioactive fission product. Though effective, KI administration needs to occur prior to or as soon as possible (within a few hours) after radioactive exposure to maximize the radioprotective benefits of KI. During the Chernobyl nuclear reactor accident, KI was not administered soon enough after radiation poisoning occurred to thousands of people. The delay in administration of KI resulted in an increased incidence of childhood thyroid cancer. Perchlorate (ClO(4)(-)) was suggested as another pharmaceutical radioprotectant for 131I- poisoning because of its ability to block thyroidal uptake of iodide and discharge free iodide from the thyroid gland. The objective of this study was to compare the ability of KI and ammonium perchlorate to reduce thyroid gland exposure to radioactive iodide (131I-). Rats were dosed with 131I- tracer and 0.5 and 3 h later dosed orally with 30 mg/kg of either ammonium perchlorate or KI. Compared to controls, both anion treatments reduced thyroid gland exposure to 131I- equally, with a reduction ranging from 65 to 77%. Ammonium perchlorate was more effective than stable iodide for whole-body radioprotectant effectiveness. KI-treated animals excreted only 30% of the (131)I(-) in urine after 15 h, compared to 47% in ammonium perchlorate-treated rats. Taken together, data suggest that KI and ammonium perchlorate are both able to reduce thyroid gland exposure to 131I- up to 3 h after exposure to 131I-. Ammonium perchlorate may offer an advantage over KI because of its ability to clear 131I- from the body.

Radioactive Iodide (131I−) Excretion Profiles in Response to Potassium Iodide (KI) and Ammonium Perchlorate (NH4ClO4) Prophylaxis

“…We evaluated the efficacy of these post-exposure treatments by monitoring 131 I − in the thyroid gland, urine, and serum for up to 3 days after dosing. This study design was based on a previous study in our laboratory [15], which showed that at 15 hours after treatment with KI or NH 4 ClO 4 , the perchlorate treated rats excreted three times the amount of 131 I − in urine compared with control treatments, while stable iodide treated rats excreted only twice the amount of 131 I − in urine compared with control treatments. In the current study, we confirm our earlier results that perchlorate treatment led to faster 131 I − excretion compared with KI treatment (Table 2).…”

“…In previous rat studies we reported that over a 15 hour post dosing period, KI and NH 4 ClO 4 were equally effective at reducing thyroid gland exposure to 131 I − [15]. However, NH 4 ClO 4 was more effective at increasing urinary clearance of 131 I − than KI.…”

“…Additionally, perchlorate administration displaces non-organified iodide from the thyroid, and the perchlorate discharge test has been used to diagnose iodide organification defects in humans for decades [10]. Perchlorate has been shown to have side effects ranging from rash and fever to several fatal cases of aplastic anemia [13,14], though these effects typically manifest from large bolus doses administered over weeks or months [15]. …”

“…In a similar experiment, these authors also intravenously dosed rats with 3.3 mg/kg of isotonically labeled ClO 4 − ( 36 ClO 4 ) and reported that 96% of the dose was excreted in 24 hours and 99.5% by 48 hours [17]. In a recent study, an oral dose of 30 mg/kg of ClO 4 − was administered to rats, and 38% of the dose was recovered in urine within the first 12 hours after dosing [15]. …”

A comparison of thyroidal protection by stable iodine or perchlorate in the case of acute or prolonged radioiodine exposure

“…An alternative could be perchlorate (Harris et al 2009 ). The NI-symporter is not selective for iodide, but transports several related monovalent anions.…”