New versatile bifunctional chelating agents for developing copper radiopharmaceuticals

Radiopharmaceuticals based on metallic radionuclides, such as ^64/67Cu, ^99mTc, ^186/188Re and ^86/90Y, are often used for diagnostic and therapeutic purposes. These nuclides are usually enveloped in organic ligands, such as heteromacrocyclic systems. To be effective, the ligands have to show fast metal complexation kinetics, form complexes with high in vitro and in vivo stability and contain a group that can be linked to biomolecules. In this regard, we are developing new ligand scaffolds for copper radionuclides which satisfy these requirements. Ligands – based on hexadentate 3,7-diazabicyclo[3.3.1]nonane I (bispidine) and bis(2-pyridylmethyl) triazacyclononane (DMPTACN) II – are discussed. These derivatives allow the introduction of linker groups, such as carboxylic acids, maleinimide or isothiocyanate, thereby facilitating coupling of targeting molecules.