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 - Publisher Copyright:
© 2016 American Chemical Society.
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
SN - 0020-1669
VL - 55
SP - 6892
EP - 6901
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 14
ER -