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

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• 作者：Eszter Boros ; Cara L. Ferreira ; Jacqueline F. Cawthray ; Eric W. Price ; Brian O. Patrick ; Dennis W. Wester ; Michael J. Adam ; Chris Orvig
• 刊名：Journal of the American Chemical Society
• 出版年：2010
• 出版时间：November 10, 2010
• 年：2010
• 卷：132
• 期：44
• 页码：15726-15733
• 全文大小：315K
• 年卷期：v.132,no.44(November 10, 2010)
• ISSN：1520-5126

文摘

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.