Radioisotopes and Radiation in Health Sciences

The research on diagnostic imaging agents is an area of bioiorganic chemistry which includes the design of ligands, the coordination reaction between the ligands and the radionuclide, radiochemical characterization and biodistribution studies. Over the past three decades, biospecific imaging agents have evolved from large molecules to small ones with biologic activity. The coordination of a radionuclide to a ligand, imply a new molecule and consequently its biodistribution is questionable. By other side, the coordinated metal bounds should not compete with the biologic active sites. Biguanide (Big) H2N-C(=NH)-NHC(=NH)-NH2 and N-substituted derivatives are a condensed system of amidine (or guanidinum) groups, known to exhibit biologic activity by binding to phosphates and carboxilates and are nitrogen donor ligands able to coordinate transition metals. High stable complexes showing extensive electronic delocalization are described on literature. In this work the synthesis, radiochemical characterization and biodistribution studies of 99m Tc oxo and nitrido complexes with Big and derived ligands dimethyl (DMBig), phenyl (Pbig) and phenethyl (PEBig) are reported. Technetium and Rhenium in Chemistry and Nuclear Medicine, ed. M. Nicolini, G. Bandoli and U. Mazzi, SGEditoriali-Padova (1995) pg. 425-428. (Proceedings of the ―Fourth International Symposium on Technetium in Chemistry and Nuclear Medicine‖, Bressanone, Itália, 12-14, September, 1994). Correlation between lipophilicity and cardiolipin binding of 99m Tc oxo and 99m Tc nitrido complexes of biguanides M. Neves, L. Gano and L. Patrício ICEN / Dep. Radioisótopos, Extrada Nacional 10, 2685 Sacavém, Portugal Abstract The radiochemical characterization of new radiopharmaceuticals involves the evaluation of lipophilicity due the relevant role of this parameter on biological uptake. The lipophilicity is usually expressed by the partition coefficient (PC) of the radiopharmaceutical between an organic phase (octanol) and an aqueous one (saline or phosphate buffer). In such a way, there is a ―making ideia‖ that radiopharmaceuticals with high PC values would be promising perfusion imaging agents. According to Coulais et. al. (1), the brain uptake of 99m Tc oxo and 99m Tc nitrido complexes of N,N ’ ethylene bis(thioacetylacetonyldeneimine) are well correlated with their PC values. But this was not observed for ligands in which two methyl taking the place of two phenyl groups. In fact, PC of a wide number of drugs did not correlate with their binding to biologic membranes as reported by Mason et. al. (2). These authors claim that the partition of any drug in an isotropic two-phase system is not a goodThe radiochemical characterization of new radiopharmaceuticals involves the evaluation of lipophilicity due the relevant role of this parameter on biological uptake. The lipophilicity is usually expressed by the partition coefficient (PC) of the radiopharmaceutical between an organic phase (octanol) and an aqueous one (saline or phosphate buffer). In such a way, there is a ―making ideia‖ that radiopharmaceuticals with high PC values would be promising perfusion imaging agents. According to Coulais et. al. (1), the brain uptake of 99m Tc oxo and 99m Tc nitrido complexes of N,N ’ ethylene bis(thioacetylacetonyldeneimine) are well correlated with their PC values. But this was not observed for ligands in which two methyl taking the place of two phenyl groups. In fact, PC of a wide number of drugs did not correlate with their binding to biologic membranes as reported by Mason et. al. (2). These authors claim that the partition of any drug in an isotropic two-phase system is not a good