Acyclic Chelate with Ideal Properties for 68Ga PET Imaging Agent Elaboration

• Published in: Journal of the American Chemical Society 2010-11, Vol.132 (44), p.15726-15733
• Main Authors: Boros, Eszter, Ferreira, Cara L, Cawthray, Jacqueline F, Price, Eric W, Patrick, Brian O, Wester, Dennis W, Adam, Michael J, Orvig, Chris
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja106399h

We have investigated novel bifunctional chelate alternatives to the aminocarboxylate macrocycles NOTA (N3O3) or DOTA (N4O4) for application of radioisotopes of Ga to diagnostic nuclear medicine and have found that the linear N4O2 chelate H2dedpa coordinates 67Ga quantitatively to form [67Ga(dedpa)]+ after 10 min at RT. Concentration-dependent coordination to H2dedpa of either 68Ga or 67Ga showed quantitative conversion to the desired products with ligand concentrations as low as 10−7 M. With 68Ga, specific activities as high as 9.8 mCi nmol−1 were obtained without purification. In a 2 h competition experiment against human apo-transferrin, [67Ga(dedpa)]+ showed no decomposition. Two bifunctional versions of H2dedpa are also described, and these both coordinate to 67Ga at RT within 10 min. Complete syntheses, characterizations, labeling studies, and biodistribution profiles of the 67Ga complexes are presented for the new platform chelates. The stability of these platform chelates is higher than that of DOTA.