Chemical and biological evaluation of 153 Sm and 46/47 Sc complexes of indazolebisphosphonates for targeted radiotherapy.

Introduction: Novel 1-hydroxy-1,1-bisphosphonates derived from indazole and substituted at the C-3 position were labeled with the radionuclides (46)Sc and (153)Sm. Several parameters such as molar ligand concentration, pH, reaction time and temperature were studied. The radiolabelling yield, reaction kinetics and stability were assessed and radiocomplexes were evaluated by in vitro and in vivo experiments.

Methods: The radionuclides (46)Sc and (153)Sm were obtained by neutron irradiation of natural Sc(2)O(3) and enriched (152)Sm(2)O(3) (98.4%) targets at the neutron flux of 3 × 10(14) n cm(-2)s(-1). The radiolabelling yield, reaction kinetics and stability were accomplished by ascending instant thin layer chromatography. The radiocomplexes were submitted to in vitro experiments (hydroxyapatite binding and lipophilicity) and biodistribution studies in animal models.

Results: The radionuclides (46)Sc and (153)Sm were produced with specific activities of 100 and 430 MBq mg(-1), respectively. High radiochemical yields were achieved and the hydrophilic radiocomplexes have shown high degree of binding to hydroxyapatite. Biodistribution studies at 1, 3 and 24h of the 4 radiocomplexes under study, have showed a similar biodistribution profile with a relatively high bone uptake, slow clearance from blood and a very slow rate of total radioactivity excretion from the whole animal body.

Conclusion: We have developed a new class of indazolebisphosphonates complexes with radioisotopes of samarium and scandium. All complexes have shown high degree of binding to hydroxyapatite, which could be attributed to the ionized phosphonate groups. The bone uptake and the bone-to-muscle ratios were relatively low.