title: New Bifunctional Chelator p-SCN-PhPr-NE3TA for Copper-64: Synthesis, Peptidomimetic Conjugation, Radiolabeling, and Evaluation for PET Imaging.
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 (64)Cu-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 (64)Cu under mild conditions. The conjugate (64)Cu-NE3TA-PEG4-LLP2A showed significantly higher specific activity, compared with (64)Cu-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 (64)Cu-based radiopharmaceuticals.
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology , 13 Hangkong Road, Wuhan 430030, China.|Department of Radiology, University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Gai
authors.affiliation: Department of Radiology, University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Sun
authors.affiliation: College of Pharmacy, The Third Military Medical University , Chongqing 400038, China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Hui
authors.affiliation: College of Pharmacy, The Third Military Medical University , Chongqing 400038, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ouyang
authors.affiliation: Department of Radiology, University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States.|Departments of Pharmacology & Chemical Biology and Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology , 13 Hangkong Road, Wuhan 430030, China.
authors.forename: Guangya
authors.initials: G
authors.lastname: Xiang
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology , 13 Hangkong Road, Wuhan 430030, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Radiology, University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Dexing
authors.initials: D
authors.lastname: Zeng
mesh_terms: D002614:Chelating Agents / Q000737:chemistry*; D003301:Copper Radioisotopes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D057786:Peptidomimetics / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D057786:Peptidomimetics