New Bifunctional Chelator p-SCN-PhPr-NE3TA for Copper-64: Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging

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• 作者：Yongkang Gai ; Lingyi Sun ; Wenqi Hui ; Qin Ouyang ; Carolyn J. Anderson ; Guangya Xiang ; Xiang Ma ; Dexing Zeng
• 刊名：Inorganic Chemistry
• 出版年：2016
• 出版时间：July 18, 2016
• 年：2016
• 卷：55
• 期：14
• 页码：6892-6901
• 全文大小：558K
• 年卷期：0
• ISSN：1520-510X

文摘

Bifunctional chelators play an important role in developing metallic radionuclide-based radiopharmaceuticals. In this study, a new bifunctional ligand, p-SCN-PhPr-NE3TA, was synthesized and conjugated to a very late antigen-4 targeting peptidomimetic, LLP2A, for evaluating its application in ⁶⁴Cu-based positron emission tomography (PET) imaging. The new ligand exhibited strong selective coordination of Cu(II), leading to a robust Cu complex, even in the presence of 10-fold Fe(III). The LLP2A conjugate of p-SCN-PhPr-NE3TA was prepared and successfully labeled with ⁶⁴Cu under mild conditions. The conjugate ⁶⁴Cu-NE3TA-PEG₄-LLP2A showed significantly higher specific activity, compared with ⁶⁴Cu-NOTA-PEG₄-LLP2A, while maintaining comparable serum stability. Subsequent biodistribution studies and PET imaging in mice bearing B16F10 xenografts confirmed its favorable in vivo performance and high tumor uptake with low background, rendering p-SCN-PhPr-NE3TA a promising bifunctional chelator for ⁶⁴Cu-based radiopharmaceuticals.