Complexes of myo-inositol-hexakisphosphate (InsP6) with zinc or lanthanum to enhance excretion of radioactive strontium from the body

Abstract

90Sr, which was released into the atmosphere and the ocean following the Chernobyl and Fukushima Daiichi nuclear power plant disasters, is an important nuclear fission element. Compounds that inhibit the absorption of 90Sr into the bloodstream and enhance its elimination can be beneficial in decreasing the absorbed radiation dose in people exposed to 90Sr. Recently, we prepared complexes of myo-inositol-hexakisphosphate (InsP6) with zinc or lanthanum as decorporation agents. These complexes, called Zn-InsP6 and La-InsP6 respectively, are insoluble in water and can potentially chelate additional metal cations. Hypothesizing that these complexes can assist the excretion of 90Sr from the body, we evaluated them using 85Sr instead of 90Sr. In in vitro binding experiments, Zn-InsP6 showed higher strontium adsorption capacity than La-InsP6. We then performed in vivo biodistribution experiments of Zn-InsP6 in mice after oral administration of 85SrCl2. Mice treated with Zn-InsP6 showed significantly lower bone accumulation of radioactivity than mice in a non-treatment control group. Zn-InsP6 adsorbed radiostrontium in the gastrointestinal tract, inhibited this ion's absorption into the bloodstream, and enhanced its excretion in the feces. Therefore, Zn-InsP6 appears to be a promising 90Sr "decorporation" agent.

Fig 1. The structure of myo-inositol-hexakisphosphate (InsP6).

Fig 2. Langmuir model.

Adsorption capacity of (A) Zn-InsP6 and (B) La-InsP6 to strontium. Data are expressed as the mean ± SD of three samples.

Fig 3. Adsorption of ⁸⁵Sr to IP6 complexes in the presence of cations.

Binding ratios of ⁸⁵Sr²⁺ to (A) Zn-InsP6 and (B) La-InsP6 in the presence of Na⁺ or Ca²⁺. Zero additional metal concentration (white columns) means using HEPES buffer containing 10 mM Na⁺. Data are expressed as the mean ± SD of three samples. Significance was determined using one-way ANOVA followed by Dunnett’s post hoc test (*p < 0.05 vs. Control (HEPES buffer containing 10 mM Na⁺)).