Development and validation of combined in vitro and in vivo assays for evaluating the efficacy of strontium-chelating compounds

Abstract

Abstract The aim of this study is to develop a combined in vitro and in vivo assay for the comprehensive efficacy evaluation of strontium-chelating compounds. The complexation and removal of harmful radioactive strontium ( 90 Sr) from the living organism may be necessary in the event of an accidental nuclear disaster or nearby nuclear war event, to prevent its incorporation into bones and thus avoid its long-term harmful health effects. To validate the model, we used a strontium-selective chelator macrocyclic substance (Decorporol) in our measurements, which potentially could be approved as a drug without significant toxic side effects. It has been proven to effectively remove strontium before it is incorporated into bones without significantly affecting calcium homeostasis in the body, and without relevant toxicity or side effects. In this study, we established an extremely sensitive test system that allows for the examination of chelator molecules in preventing the incorporation of non-radioactive SrCl 2 into mineralized extracellular matrix in cell culture. We also optimized an in vivo mouse model suitable to investigate strontium incorporation and the effect of chelators. These assays also provide an opportunity for the safe evaluation of similar compounds.