In a quest for more effective radiopharmaceuticals for palliation of pain experienced by metastatic bone cancer patients, results obtained with the therapeutic radionuclides 153 SM, 166 Ho and 117mSn complexed to bone-seeking phopsphate ligands are related. As phosphonates are known to enhance the remodelling of bone and to have the ability to act as bone cancer pain palliation agents, they were the ideal starting point of our search. Models for speciation of components in blood plasma were constructed by including the measured blood plasma metal-ions, Ca, Mg, Zn, as well as Sm. The formation constants were measured by glass electrode potentiometry or polarography, or if necessary estimated by linear free energy plots (LFER). For the blood plasma models the computer programme ECCLES was used. Using these models the biodistribution or radiopharmaceuticals in blood plasma could be evaluated and explanations found for their in vivo behaviour. Although blood plasma spectation models, based on thermodynamic considerations, only indicate in what species a radiopharmaceutical will be present in blood plasma, they were able to provide insight into in vivo behaviour of the proposed bone seeking radiopharmaceuticals and how a future radiopharmaceuticals should be designed. This approach will be illustrated at the hand of newly designed radiopharmaceuticals as well as results achieved by others.Interfaculty Reactor Institut