Technetium coordination state as a factor of stability in 99mTc-complexes used in hepatobiliary system: comparative studies on 99mTc-complexes of pyridoxal with glutamate (Tc-PG) and isoleucine (Tc-PI).

Studies on 99mTc-Penicillamine (Tc-Pen) have given us some insight into the significance of the technetium coordination state in hepatobiliary clearance behavior. A 99mTc-complex of pyridoxal and glutamate (Tc-PG) prepared by Baker et al. (1975) using an autoclaving process or by a Sn-Resin kit method (Horiuchi 1981) was compared with a 99mTc-complex of pyridoxal and isoleucine (Tc-PI) prepared by the method of Kato and Hazue (1978) through an intermediate compound of stannous ion, at room temperature. Tc-PG and TcPI complexes analyzed by thin layer chromatography, sephadex column chromatography (G-15), octanol extraction, and ligand exchange reaction showed different chemical properties. Their biological evaluation also demonstrated great differences in biodistribution in mice, metabolic studies, protein binding, and rat bile excretion. Tc-PG was estimated as an hepatobiliary agent with strong metal-ligand binding, inert to ligand exchange reaction with Pen at physiological pH; the likely occurrence of technetium in a mononuclear or dinuclear state providing the great stability observed in its biological and in vivo behavior was compared with the relatively weaker binding observed in Tc-PI, a highly lipophilic complex of high liver partition but of low stability, denoting its different chemical characteristics. The technetium coordination state in radiopharmaceuticals is responsible for the integrity of the molecule while in the blood pool and its relevance in impaired liver uptake is discussed.