New directions in the coordination chemistry of 99mTc: a reflection on technetium core structures and a strategy for new chelate design.

Bifunctional chelates offer a general approach for the linking of radioactive metal cations to macromolecules. In the specific case of 99mTc, a variety of technologies have been developed for assembling a metal-chelate-biomolecule complex. An evaluation of these methodologies requires an appreciation of the coordination characteristics and preferences of the technetium core structures and oxidation states, which serve as platforms for the development of the imaging agent. Three technologies, namely, the MAG3-based bifunctional chelates, the N-oxysuccinimidylhydrazino-nicotinamide system and the recently described single amino acid chelates for the {Tc(CO)3}1+ core, are discussed in terms of the fundamental coordination chemistry of the technetium core structures. In assessing the advantages and disadvantages of these technologies, we conclude that the single amino acid analogue chelates (SAAC), which are readily conjugated to small peptides by solid-phase synthesis methods and which form robust complexes with the {Tc(CO)3}1+ core, offer an effective alternative to the previously described methods.