New Bifunctional Chelator p-SCN-PhPr-NE3TA for Copper-64

Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging

Yongkang Gai, Lingyi Sun, Wenqi Hui, Qin Ouyang, Carolyn J. Anderson, Guangya Xiang, Xiang Ma, Dexing Zeng

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)6892-6901
Number of pages10
JournalInorganic Chemistry
Volume55
Issue number14
DOIs
StatePublished - Jul 18 2016
Externally publishedYes

Fingerprint

Peptidomimetics
Positron emission tomography
Radiopharmaceuticals
Chelating Agents
conjugation
Copper
positrons
Bearings (structural)
tomography
Integrin alpha4beta1
Ligands
Imaging techniques
copper
ligands
evaluation
antigens
synthesis
Heterografts
Radioisotopes
serums

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 journalArticle

Gai, Yongkang ; Sun, Lingyi ; Hui, Wenqi ; Ouyang, Qin ; Anderson, Carolyn J. ; Xiang, Guangya ; Ma, Xiang ; Zeng, Dexing. / New Bifunctional Chelator p-SCN-PhPr-NE3TA for Copper-64 : Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging. In: Inorganic Chemistry. 2016 ; Vol. 55, No. 14. pp. 6892-6901.
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