Complexes of low energy beta emitters 47Sc and 177Lu with zoledronic acid for bone pain therapy

Targeted radiopharmaceuticals have been mostly developed to visualize and/or treat oncologic diseases. In targeted radiotherapy radionuclide selection is a key issue, because the radionuclide should provide the appropriate radiation absorbed dose, matching the desirable biologic effect, but at the same time it should preclude irradiation of surrounding healthy tissues. Among the last generation of bisphosphonates with cyclic side chains, zoledronic acid is the most potent bisphosphonate, described till now, which inhibits bone resorption. In this paper, we describe the synthesis, properties and hydroxyapatite binding of zoledronic acid labeled with two low energy beta emitters, (47)Sc and (177)Lu. Radiochemicals labeled with low energy electron emitters are preferred, because they deliver both a therapeutic dose to the bone and spare the bone marrow. Hydroxyapatite adsorption experiments have shown that the binding values obtained with complexes of zoledronic acid labeled with (46)Sc and (177)Lu are much higher than those of bisphosphonates labeled with (153)Sm and (166)Ho. Hence, complexes of zoledronic acid with either (46)Sc or (177)Lu seems to be a promising radiopharmaceutical for bone pain therapy.