Evaluation of H2CHXdedpa, H2dedpa- and H2CHXdedpa-N, N′-propyl-2-NI ligands for 64Cu(ii) radiopharmaceuticals. Issue 33 (10th May 2016)

• Record Type: Journal Article
• Authors: Ramogida, Caterina F.; Boros, Eszter; Patrick, Brian O.; Zeisler, Stefan K.; Kumlin, Joel; Adam, Michael J.; Schaffer, Paul; Orvig, Chris
• Is Part Of: Dalton transactions. Volume 45:Issue 33(2016)
• Page Start: 13082
• Page End: 13090
• Publication Date: 2016-05-10
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c6dt00932h
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Hexadentate acyclic chelate H2 CHX dedpa and related N, N ′-alkylated ligands are radiolabeled with radioactive 64 Cu(ii ) under mild conditions forming kinetically inert complexes. Abstract : The chiral acyclic "pa" ligand (pa = picolinic acid) H2 CHX dedpa (N4 O2 ) and two NI-containing dedpa analogues (H2 CHX dedpa- N, N ′-propyl-2-NI, H2 dedpa- N, N ′-propyl-2-NI, NI = nitroimidazole) were studied as chelators for copper radiopharmaceuticals ( CHX = cyclohexyl, H2 dedpa = 1, 2-[[carboxypyridin-2-yl]methylamino]ethane). The hexadentate ligand H2 CHX dedpa was previously established as a superb system for 67/68 Ga radiochemistry. The solid state X-ray crystal structures of [Cu( CHX dedpa- 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 CHX dedpa 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( CHX dedpa)] was found to be 98% stable compared to previously investigated [ 64 Cu(dedpa)] which was only 72% intact after 24 hours.