title: Novel hexadentate and pentadentate chelators for ⁶⁴Cu-based targeted PET imaging.
abstract: A series of new hexadentate and pentadentate chelators were designed and synthesized as chelators of (64)Cu. The new pentadentate and hexadentate chelators contain different types of donor groups and are expected to form neutral complexes with Cu(II). The new chelators were evaluated for complex kinetics and stability with (64)Cu. The new chelators instantly bound to (64)Cu with high labeling efficiency and maximum specific activity. All (64)Cu-radiolabeled complexes in human serum remained intact for 2 days. The (64)Cu-radiolabeled complexes were further challenged by EDTA in a 100-fold molar excess. Among the (64)Cu-radiolabeled complexes evaluated, (64)Cu-complex of the new chelator E was well tolerated with a minimal transfer of (64)Cu to EDTA. (64)Cu-radiolabeled complex of the new chelator E was further evaluated for biodistribution studies using mice and displayed rapid blood clearance and low organ uptake. (64)Cu-chelator E produced a favorable in vitro and in vivo complex stability profiles comparable to (64)Cu complex of the known hexadentate NOTA chelator. The in vitro and in vivo data highlight strong potential of the new chelator E for targeted PET imaging application.
authors.affiliation: Chemistry Division, Department of Biological and Chemical Sciences, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL 60616, United States.
authors.forename: Inseok
authors.initials: I
authors.lastname: Sin
authors.affiliation: Chemistry Division, Department of Biological and Chemical Sciences, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL 60616, United States.
authors.forename: Chi Soo
authors.initials: CS
authors.lastname: Kang
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Nilantha
authors.initials: N
authors.lastname: Bandara
authors.affiliation: Chemistry Division, Department of Biological and Chemical Sciences, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL 60616, United States.
authors.forename: Xiang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Chemistry Division, Department of Biological and Chemical Sciences, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL 60616, United States.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Buck E
authors.initials: BE
authors.lastname: Rogers
authors.affiliation: Chemistry Division, Department of Biological and Chemical Sciences, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL 60616, United States. Electronic address: Chong@iit.edu.
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Chong
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D003301:Copper Radioisotopes / Q000737:chemistry; D005260:Female; D006801:Humans; D051379:Mice; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals
keywords: (64)Cu; Chelating agents; NOTA; PET imaging