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

In the quest for more effective pain palliation radiopharmaceuticals for me tastatic bone cancer, this paper relates results obtained with Ho-166 compl exed to the bone-seeking bisphosphonate, 1-hydroxy-4-aminopropylidenediphos phonate (APD). APD is itself a bone cancer pain palliation agent and this w ork was therefore driven by the idea that the energetic beta-particle emitt er, Ho-166, coupled with APD could afford a highly effective radiopharmaceu tical in the treatment of bone cancer; Complex-formation constants for impo rtant blood plasma metal-ions were measured by potentiometry or polarograph y at 37 degrees C and I = 150 mmol dm(-3). The latter technique was used fo r systems where precipitates formed at ligand-to-metal ratios appropriate f or potentiometry. For trivalent lanthanides, neither electrochemical techni que could be used. Animal tests showed that the Ho-166-APD complex was take n up primarily by the liver due to precipitation or colloid formation. (C) 1999 Elsevier Science Inc. All rights reserved.