Metal-ion speciation in blood plasma incorporating the bisphosphonate, 1-hydroxy-4-aminopropilydenediphosphonate (APD), in therapeutic radiopharmaceuticals

Abstract

In the quest for more effective pain palliation radiopharmaceuticals for metastatic bone cancer, this paper relates results obtained with 166Ho complexed to the bone-seeking bisphosphonate, 1-hydroxy-4-aminopropylidenediphosphonate (APD). APD is itself a bone cancer pain palliation agent and this work was therefore driven by the idea that the energetic β-particle emitter, 166Ho, coupled with APD could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants for important blood plasma metal-ions were measured by potentiometry or polarography at 37°C and I=150 mmol dm −3. The latter technique was used for systems where precipitates formed at ligand-to-metal ratios appropriate for potentiometry. For trivalent lanthanides, neither electrochemical technique could be used. Animal tests showed that the 166Ho–APD complex was taken up primarily by the liver due to precipitation or colloid formation.