Octadentate Oxine-Armed Bispidine Ligand for Radiopharmaceutical Chemistry

In this study, we present the synthesis and characterization of the octadentate bispidine ligand, H₂bispox² and its complexes with medicinally useful radiometal nuclides (¹¹¹In³⁺ and ¹⁷⁷Lu³⁺), including their X-ray diffraction single crystal structures with the stable isotopes. ¹¹¹InCl₃ radiolabels the ligand quantitatively at ambient conditions ([L] = 10^-5 M, room temperature, pH 7 and 15 min) and the in vitro human serum stability assays demonstrated high stability of the [¹¹¹In(bispox²)]⁺ complex over 5 days. Moreover, the β ^- emitter ¹⁷⁷Lu radiolabels the ligand at 37 °C in 30 min (pH 8). These initial investigations reveal the potential of the octadentate bispidine ligand H₂bispox² as a useful chelator for ¹¹¹In and ¹⁷⁷Lu-based radiopharmaceuticals.