fac-[TcO₃(tacn)]+: A Versatile Precursor for the Labelling of Pharmacophores, Amino Acids and Carbohydrates through a New Ligand-Centred Labelling Strategy

摘要

Herein, we report a protocol for the synthesis of [99mTcO₃(tacn)]+ ([1]+) (tacn=1,4,7-triazacyclononane) that is suitable for clinical translation. Bioconjugates containing pharmacophores ([TcO(NO₂-Imi)(tacn)]+; [3]+), artificial amino acids ([TcO(Fmoc-allyl-His)(tacn)]+; [5]+), and glucose derivatives ([TcO(allyl-tetraacetylglucose)(tacn)]+; [7]+) were synthesized by cycloaddition strategies and fully characterized (99Tc and 99mTc). 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 [99mTcO(NO₂-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 [99mTcO₃(tacn)]+ building block is a complement to the complexes of the fac-{Tc(CO)₃}+ core.