title: fac-[TcO3(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(Fmoc-allyl-His)(tacn)](+); [5](+)), and glucose derivatives ([TcO(allyl-tetraacetylglucose)(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.
authors.affiliation: Institute of Inorganic Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. braband@aci.uzh.ch
authors.forename: Henrik
authors.initials: H
authors.lastname: Braband
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tooyama
authors.forename: Thomas
authors.initials: T
authors.lastname: Fox
authors.forename: Ryan
authors.initials: R
authors.lastname: Simms
authors.forename: John
authors.initials: J
authors.lastname: Forbes
authors.forename: John F
authors.initials: JF
authors.lastname: Valliant
authors.forename: Roger
authors.initials: R
authors.lastname: Alberto
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D005947:Glucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000596:Amino Acids; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D005947:Glucose