The chemical identity of pentavalent technetium-99m-dimercaptosuccinic acid

Abstract

The tumor-targeting radiopharmaceutical known as pentavalent technetium-99m-meso dimercaptosuccinic acid (DMSA) has been studied by a variety of techniques in order to elucidate its structure and chemical behavior. The radiopharmaceutical is identical with a chemically characterized sample of [99TcO(DMSA)2]- when studied by mobility methods including thin-layer chromatography, reversed-phase high-performance liquid chromatography, gel filtration, and electrophoresis. The technetium is pentavalent and coordinated by an oxo-ligand and four thiolate sulfurs of two DMSA ligands. No-carrier-added preparations consist of mixtures of three stereoisomers of the square pyramidal, mononuclear complex. The isomers arise from differing orientations of the carboxylate groups in the DMSA ligands and may be designated syn-endo, syn-exo, and anti. All three isomers are significant components of the radiopharmaceutical, raising the question of which are tumor-specific. The carboxylate groups in the complex are almost completely ionized at pH 7, thus the average charge on the complex at this pH approaches -5.