fac-TcO(3)(tacn)](+): A versatile precursor for the labelling of pharmacophores, amino acids and carbohydrates through a new ligand-centred labelling strategy

Abstract

Herein, we report a protocol for the synthesis of (99m)TcO(3)(tacn)](+) (1](+)) (tacn=1,4,7-triazacyclononane) that is suitable for clinical translation. Bioconjugates containing pharmacophores (TcO(NO(2)-Imi)(tacn)](+); 3](+)), artificial amino acids (TcO(Fmocallyl-His)(tacn)](+); 5](+)), and glucose derivatives (TcO(allyl-tetraacetyl-glucose) (tacn)](+); 7](+)) were synthesized by cycloaddition strategies and fully characterized ((99)Tc and (99m)Tc). These new technetium complexes are stable at neutral pH and demonstrate the potential and flexibility of the 3+2] cycloaddition labelling concept. In addition to the synthetic work, the first biodistribution studies of 1]+ and the small 3+2] cycloadduct (99m)TcO(NO(2)-Imi)(tacn)](+) (3](+)) were completed. The biodistribution studies suggest the stability of these complexes in vivo. Furthermore, it was demonstrated that the high hydrophilicity of the (99m)TcO(3)(tacn)](+) building block is a complement to the complexes of the fac-{Tc(CO)(3)}(+) core.