Establishing a blood plasma model for Sn(IV) with the two blood plasma ligands, Cysteine and Histidine

Abstract

Bone pain secondary to metastatic bone cancer is the most common intractable pain and is a cause for major concern in most oncology units the world over. Bone metastasis occurs when cancerous cells from the primary tumor relocate to the bone. There have been several traditional methods of treating cancer, which included surgery, radiation and chemotherapy. However, revolutionary treatments are now under development, and researchers are now using laboratory discoveries to design drugs that will exploit specific biological processes in cancer. Presently bone seeking radiopharmaceuticals have proven to be a promising modality in the treatment of metastatic bone cancer, but patients require more effective radiopharmaceuticals for not only pain palliation, but also stopping the spread of this cancer. In the mission to identify those radiopharmaceuticals, ongoing research involves a trial and error approach to find the drug that will interact more effectively and selectively with the tumor. There are factors that should be taken into consideration when analyzing the rad iopharmaceutical, namely the pharmacological and chemical properties of the drug. The speciation studies have shown that [1 17mSn]Sn(IV)-PEI-MP complexes could prove more effective in delivering antitumor effect in bone lesions, but the exact mode of action of the Sn(IV) is not known in the blood plasma. This does not limit its therapeutic usefulness and the only way to avoid, control, and counteract harmful drug effects depends on a good understanding of the mechanism involved. On the basis of this knowledge, it is possible to control the toxicity, if present, or decide whether to proceed with the administration of the drug in patients. Since the discovery that the blood plasma ligands can compete with the metal-ion in vivo for complexation, an effort was made to determine the binding interaction for the complexation of Cysteine and Histidine with Sn(IV) in this study. The formation constants were determined using potentiometry and a computational modeling program ESTA (Equilibrium Simulation by Titration Analysis). The

outcomes have shown that the complexation of both ligands with Sn(IV) results in the formation of hydroxyl species.