Hampa─Versatile Chelator for [Pb]Pb, [Bi]Bi, and [Ac]Ac.

A new decadentate chelator, Hampa, was designed to be a potential radiopharmaceutical chelator component. The chelator involves both amide and picolinate functional groups on a large non-macrocyclic, ether-bridged backbone. With its large scaffold, Hampa was paired with [Pb]Pb, [Bi]Bi, and La/[Ac]Ac ions. Nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry were used to study the non-radioactive metal complexes. A single crystal of Bi(ampa) was obtained; its asymmetric, 10-coordinate complex structure was revealed by X-ray diffraction. Optimal conformations of the metal complexes were assessed by density functional theory studies to provide further structural information. Solution studies providing thermodynamic insights into metal complex formation revealed Hampa coordinated Bi, Pb, and La ions to obtain pM values of 26, 14.8, and 15.1, respectively. Preliminary concentration-dependent radiolabeling experiments were carried out between Hampa and three different radiometals to evaluate their compatibility for radiopharmaceutical applications. The chelator radiolabeled [Pb]Pb, [Bi]Bi, and [Ac]Ac in short reaction times (7-30 min), at dilute concentrations, and under mild conditions. Thus, Hampa was proven to be a versatile chelator able to well coordinate a small range of radiometals frequently considered to be alpha therapeutic candidates.