Estimating protein binding upon treatment with radionuclide ions

Several types of radioactive isotopes are used for cancer treatment. While most are embedded in chelating agents, ²²³Ra is given as RaCl₂ salt and ⁹⁰Y in microspherical particles. If ionic radionuclides are free, they have the potential to bind to proteins instead of their endogenous ions, interfere with their activity and be transported by them. In this study, a computational approach was used to estimate the binding affinities of Y³⁺, Ra²⁺ and Pb²⁺ (²⁰⁷Pb is the decay product of ²²³Ra) to proteins, instead of their native cofactors Ca²⁺ and Mn²⁺. Y³⁺ was found to bind strongly to proteins with the ability to replace Ca²⁺ and to some degree also Mn²⁺. Ra²⁺ does not bind to the studied proteins but Pb²⁺ can replace Ca²⁺ in Ca²⁺ binding proteins. A recently identified coordination compound was found to be highly selective for ²²³Ra.