H4octox: Versatile Bimodal Octadentate Acyclic Chelating Ligand for Medicinal Inorganic Chemistry

H4octox, a versatile new octadentate acyclic chelating ligand, has been investigated as an alternative to the acyclic DTPA and the macrocyclic DOTA for trivalent metal ions useful in diagnostic medical imaging or therapeutic applications (Y3+, In3+, La3+, Gd3+, Lu3+). The synthesis of H4octox is straightforward in less steps and thus more economical than those of most previously reported chelators. Complex formation equilibria in the presence of Y3+, In3+, La3+, Gd3+, and Lu3+ revealed fast chelation and high metal-sequestering capacity. Quantitative labeling with 111In3+ was achieved within 15 min at room temperature at ligand concentrations as low as 10–7 M, exactly the properties required for the development of kit-based radiopharmaceuticals. In vitro serum stability studies and in vivo SPECT imaging confirmed excellent complex stability of [111In(octox)]−. Moreover, it is more lipophilic than most of the multidentate carboxylate- or picolinate-based chelators; it therefore shows more liver clearance a...