Technetium-99m exchange labeling of sensitive molecules

Considerable interest hnas been shown by researchers in radiolabelling biologically interesting and often complex molecules with technetium-99m (Tc-99m) to detect and study various disease states in vivo. Examples of such molecules include enzymes, metabolic substrates such as glucose, ligands that bind to inter- and extracellular receptors, and monoclonal antibodies. Unfortunately many of these potentially useful compounds contain functional groups essential for maintaining biological activity which do not tolerate conventional Tc-99m labeling techniques that employ reducing conditions. The authors report on a new labeling technique which avoids having to expose sensitive target molecules to reducing agents. Moreover, the technique has the potential for being applied to a wide variety of biologically useful molecules. The method employs the concept of exchange labeling. A strong chelator which is covalently bound to the target molecule extracts the metal from a suitable labile Tc-99m complex in which the metal exists in a reduced oxidation state. The authors have found, for example, that the technetium(V) moiety in the no carrier added N-methyl N,N'-bis(2-hydroxyethyl)ethylenediamine complex is transferred quantitatively to functionalized, N,N '-bis(2-mercaptoethyl)ethylenediamine ligands within an hour at concentrations below l0/sup -6/M. The optimum choice of chelate, labile Tc-99m complex, and exchange conditions depends upon a variety of factors which are currently being studied and evaluated