Evaluation of the H2dedpa Scaffold and its cRGDyK Conjugates for Labeling with 64Cu

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• 作者：Eszter Boros ; Jacqueline F. Cawthray ; Cara L. Ferreira ; Brian O. Patrick ; Michael J. Adam ; Chris Orvig
• 刊名：Inorganic Chemistry
• 出版年：2012
• 出版时间：June 4, 2012
• 年：2012
• 卷：51
• 期：11
• 页码：6279-6284
• 全文大小：268K
• 年卷期：v.51,no.11(June 4, 2012)
• ISSN：1520-510X

文摘

Studies of the acyclic ligand scaffold H₂dedpa and its derivatives with the peptide cRGDyK for application in copper radiopharmaceuticals are described. Previously shown to be a superb ligand for ^67/68Ga, the chelate is now shown to coordinate ⁶⁴Cu in its derivatized and nonderivatized forms rapidly under mild reaction conditions (10 min, RT, pH 5.5 10 mM sodium acetate buffered solution). The hexadentate, distorted octahedral coordination of H₂dedpa is confirmed in the corresponding solid state X-ray crystal structure of [Cu(dedpa)]. Cyclic voltammetry determined the reduction potential of [Cu(dedpa)] to be below values found for common bioreductants. Reduction and reoxidation were irreversible but reproducible, indicating a potential change of coordination mode upon reduction of Cu(II) to Cu(I). The thermodynamic stability constant log K_CuL was determined to be 19.16(5), comparable to other frequently used ⁶⁴Cu chelates. Serum stability of the ⁶⁴Cu labeled chelate revealed only 3% transchelation/association to serum proteins after 2 h, while the conjugates reveal 10% ([Cu(RGD1)]) and 6% ([Cu(RGD2)]) transchelation at the same time point.