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Dalton Trans. 2016 Aug 16;45(33):13082-90. doi: 10.1039/c6dt00932h.

Evaluation of H2CHXdedpa, H2dedpa- and H2CHXdedpa-N,N'-propyl-2-NI ligands for (64)Cu(ii) radiopharmaceuticals.

Author information

1
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.
2
Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, CanadaV6T 1Z1. orvig@chem.ubc.ca.
3
Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, CanadaV6T 2A3.

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.

PMID:
27161975
DOI:
10.1039/c6dt00932h
[Indexed for MEDLINE]

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