title: Evaluation of H2CHXdedpa, H2dedpa- and H2CHXdedpa-N,N'-propyl-2-NI ligands for (64)Cu(ii) radiopharmaceuticals.
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.
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, CanadaV6T 1Z1. orvig@chem.ubc.ca and Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, CanadaV6T 2A3.
authors.forename: Caterina F
authors.initials: CF
authors.lastname: Ramogida
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, CanadaV6T 1Z1. orvig@chem.ubc.ca and Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, CanadaV6T 2A3.
authors.forename: Eszter
authors.initials: E
authors.lastname: Boros
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, CanadaV6T 1Z1. orvig@chem.ubc.ca.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Patrick
authors.affiliation: Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, CanadaV6T 2A3.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Zeisler
authors.affiliation: Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, CanadaV6T 2A3.
authors.forename: Joel
authors.initials: J
authors.lastname: Kumlin
authors.affiliation: Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, CanadaV6T 2A3.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Adam
authors.affiliation: Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, CanadaV6T 2A3.
authors.forename: Paul
authors.initials: P
authors.lastname: Schaffer
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, CanadaV6T 1Z1. orvig@chem.ubc.ca.
authors.forename: Chris
authors.initials: C
authors.lastname: Orvig
mesh_terms: D002614:Chelating Agents / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D005021:Ethylamines / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009593:Nitroimidazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D044967:Serum / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D005021:Ethylamines; D008024:Ligands; C000596869:N,N'-((6-carboxylato)pyridin-2-yl)methyl)-1,2-diaminoethane; D009593:Nitroimidazoles; D011725:Pyridines; D019275:Radiopharmaceuticals; D003300:Copper