1. Evaluation of H2CHXdedpa, H2dedpa- and H2CHXdedpa-N,Nā²-propyl-2-NI ligands for 64Cu(<scp>ii</scp>) radiopharmaceuticals
- Author
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Stefan K. Zeisler, Eszter Boros, Brian O. Patrick, Chris Orvig, Paul Schaffer, Michael J. Adam, Caterina F. Ramogida, and Joel Kumlin
- Subjects
Serum ,Pyridines ,Inorganic chemistry ,chemistry.chemical_element ,Crystal structure ,Picolinic acid ,Ligands ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Redox ,Inorganic Chemistry ,chemistry.chemical_compound ,Coordination Complexes ,Ethylamines ,Humans ,Chelation ,Chelating Agents ,Nitroimidazole ,010405 organic chemistry ,Ligand ,Copper ,0104 chemical sciences ,chemistry ,Nitroimidazoles ,Radiopharmaceuticals ,Cyclic voltammetry - Abstract
The chiral acyclic "pa" ligand (pa = picolinic acid) H2CHXdedpa (N4O2) and two NI-containing dedpa analogues (H2CHXdedpa-N,N'-propyl-2-NI, H2dedpa-N,N'-propyl-2-NI, NI = nitroimidazole) were studied as chelators for copper radiopharmaceuticals (CHX = cyclohexyl, H2dedpa = 1,2-[[carboxypyridin-2-yl]methylamino]ethane). The hexadentate ligand H2CHXdedpa was previously established as a superb system for (67/68)Ga radiochemistry. The solid state X-ray crystal structures of [Cu(CHXdedpa-N,N'-propyl-2-NI)] and [Cu(dedpa-N,N'-propyl-2-NI)] reveal the predicted hexadentate, distorted octahedral binding of the copper(ii) ion. Cyclic voltammetry of [Cu(dedpa-N,N'-propyl-2-NI)] shows that there is one reversible couple associated with the NI redox, and one irreversible but reproducible couple attributed to the Cu(ii)/Cu(i) redox cycle. Quantitative radiolabeling (99%) of CHXdedpa(2-) and (dedpa-N,N'-propyl-2-NI)(2-) with (64)Cu was achieved under fast and efficient labeling conditions (10 min, RT, 0.5 M sodium acetate buffer, pH 5.5) at ligand concentrations as low as 10(-6) M. In vitro kinetic inertness studies of the (64)Cu labelled complexes were studied in human serum at 37 °C over 24 hours; [(64)Cu(CHXdedpa)] was found to be 98% stable compared to previously investigated [(64)Cu(dedpa)] which was only 72% intact after 24 hours.
- Published
- 2016