|Title||H2ampa─Versatile Chelator for [203Pb]Pb2+, [213Bi]Bi3+, and [225Ac]Ac3+|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Ingham, A, Wharton, L, Sayed, TEl, Southcott, L, McNeil, BL, Ezhova, MB, Patrick, BO, Jaraquemada-Pelaez, Mde Guadalu, Orvig, C|
A new decadentate chelator, H2ampa, 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, H2ampa was paired with [nat/203Pb]Pb2+, [nat/213Bi]Bi3+, and natLa3+/[225Ac]Ac3+ 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)](NO3) 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 H2ampa coordinated Bi3+, Pb2+, and La3+ ions to obtain pM values of 26, 14.8, and 15.1, respectively. Preliminary concentration-dependent radiolabeling experiments were carried out between H2ampa and three different radiometals to evaluate their compatibility for radiopharmaceutical applications. The chelator radiolabeled [203Pb]Pb2+, [213Bi]Bi3+, and [225Ac]Ac3+ in short reaction times (7–30 min), at dilute concentrations, and under mild conditions. Thus, H2ampa was proven to be a versatile chelator able to well coordinate a small range of radiometals frequently considered to be alpha therapeutic candidates.