TY - JOUR
T1 - New Bifunctional Chelator p-SCN-PhPr-NE3TA for Copper-64
T2 - Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging
AU - Gai, Yongkang
AU - Sun, Lingyi
AU - Hui, Wenqi
AU - Ouyang, Qin
AU - Anderson, Carolyn J.
AU - Xiang, Guangya
AU - Ma, Xiang
AU - Zeng, Dexing
N1 - Funding Information:
This work was supported by the National Institute of Biomedical Imaging and Bioengineering (Grant No. R21- EB017317). It was also partially supported by Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20120142120095), the Fundamental Research Fund for the Central Universities (Nos. 2016YXMS140 and 2014TS090). Small animal PET/CT imaging at UPCI was supported in part by UPCI CCSG (No. P30CA047904).
Publisher Copyright:
© 2016 American Chemical Society.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2016/7/18
Y1 - 2016/7/18
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.inorgchem.6b00395
DO - 10.1021/acs.inorgchem.6b00395
M3 - Article
C2 - 27347690
AN - SCOPUS:84978779843
VL - 55
SP - 6892
EP - 6901
JO - Inorganic Chemistry
JF - Inorganic Chemistry
SN - 0020-1669
IS - 14
ER -