Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6892-6901 |
| Number of pages | 10 |
| Journal | Inorganic Chemistry |
| Volume | 55 |
| Issue number | 14 |
| DOIs | |
| State | Published - Jul 18 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Inorganic Chemistry
Cite this
New Bifunctional Chelator p-SCN-PhPr-NE3TA for Copper-64 : Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging. / Gai, Yongkang; Sun, Lingyi; Hui, Wenqi; Ouyang, Qin; Anderson, Carolyn J.; Xiang, Guangya; Ma, Xiang; Zeng, Dexing.
In: Inorganic Chemistry, Vol. 55, No. 14, 18.07.2016, p. 6892-6901.Research output: Contribution to journal › Article
}
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
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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UR - http://www.scopus.com/inward/citedby.url?scp=84978779843&partnerID=8YFLogxK
U2 - 10.1021/acs.inorgchem.6b00395
DO - 10.1021/acs.inorgchem.6b00395
M3 - Article
VL - 55
SP - 6892
EP - 6901
JO - Inorganic Chemistry
JF - Inorganic Chemistry
SN - 0020-1669
IS - 14
ER -