AAZTA: The rise of mesocyclic chelating agents for metal coordination in medicine

The application of metal ions for diagnostic and therapeutic purposes is nowadays a well consolidated practice in current medicine. Gd3+ for magnetic resonance imaging (MRI), Ga3+ for positron emission tomography (PET), In3+ for single photon emission computed tomography (SPECT) and the b-emitter Lu3+ for tumour treatment are the most representative examples. Metal ions employed in medicine must be administered as stable and inert metal complexes, mainly for safety reasons and targeting purposes. In the last years many new chelating agents have been designed, prepared and studied in order to improve properties such as thermodynamic stability, kinetic inertness, target selectivity and many other characteristics of complexes thereof. The structure of these chelating agents is almost invariably based on linear or macrocyclic backbones. The chelating agent AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid), featuring a mesocyclic 7-membered ring has found steadily increasing attention since its inception in the early 2000s and is now an affirmed alternative for the formation of stable complexes with several metal ions. The scope of this review is to provide the reader with a comprehensive survey on the synthesis and the applications of AAZTA and its derivatives developed in the last two decades.