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.