Synthesis, characterization and biodistribution of bisphosphonates Sm-153 complexes: correlation with molecular modeling interaction studies.

Bisphosphonates (BPs) are characterized by a P-C-P backbone structure and two phosphonic acid groups bonded to the same carbon, and are established as osteoclast-mediated bone resorption inhibitors. The nature of the groups attached to the central carbon atom are responsible in determining the potency of bisphosphonates as anti-resorption drugs. However, it is not yet clear the exact relationship between their molecular structure and pharmacologic activities. In this study, molecular geometries of pamidronate, alendronate and neridronate, differing only in the length of the aliphatic chains, were predicted by molecular mechanics and their interactions with hydroxyapatite, the main bone mineral component, were examined. We report the synthesis and radiochemical characterization of 153Sm complexes with pamidronate, alendronate and neridronate. Hydroxyapatite binding and biodistribution studies of these complexes have shown a good correlation with the theoretical molecular modeling interaction studies. So, it is possible to conclude that computational chemistry techniques are a good approach to evaluate specific interactions and may play a relevant role in determining the relative ability of BPs to mineral bone, and open new perspectives to the design of new BPs with increased pharmacological activity. These techniques could be extended to BPs as ligands to carrier radioactive metals, aiming for new bone therapeutic radiopharmaceuticals.

[Nationally produced 153SmEDTMP in the palliative treatment of metastatic bone cancer pain]. / 153SmEDTMP de producción nacional en el tratamiento paliativo del dolor óseo metastásico.

153SmEDTMP was obtained from enriched 152Sm irradiated at the 5 MW Chilean Research Reactor and labelled at a molar ratio of 15:1 pH 7.5. Biodistribution, autoradiography, radiochemical purity tests were done for evaluation. 40 patients were treated with 37-55 MBq/kg weight. Bone scans using 99mTcHMDP were obtained prior and after treatment. Bone marrow depression was observed in 37% of them and normal liver function in all of them. In 45% the pain dissapear completely, in 22.5% significantly decreased and partially in 30%. In 17 patients more than one dosis was injected. Our preliminary results indicate that 153SmEDTMP is a promising radiotherapeutic agent for palliative treatment of metastatic bone cancer pain and encourage its use specially because it can be produced in countries with low economic resources, thus a large number of patients can get the benefits of this new procedure.