title: Transferrin conjugates of triazacyclononane-based bifunctional NE3TA chelates for PET imaging: Synthesis, Cu-64 radiolabeling, and in vitro and in vivo evaluation.
abstract: Three different polyaminocarboxylate-based bifunctional NE3TA (7-[2-[carboxymethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) chelating agents were synthesized for potential use in copper 64-PET imaging applications. The bifunctional chelates were comparatively evaluated using transferrin (Tf) as a model targeting vector that binds to the transferrin receptor overexpressed in many different cancer cells. The transferrin conjugates of the NE3TA-based bifunctional chelates were evaluated for radiolabeling with (64)Cu. In vitro stability and cellular uptake of (64)Cu-radiolabeled conjugates were evaluated in human serum and prostate (PC-3) cancer cells, respectively. Among the three NE3TA-Tf conjugates tested, N-NE3TA-Tf was identified as the best conjugate for radiolabeling with (64)Cu. N-NE3TA-Tf rapidly bound to (64)Cu (>98% radiolabeling efficiency, 1min, RT), and (64)Cu-N-NE3TA-Tf remained stable in human serum for 2days and demonstrated high uptake in PC-3 cancer cells. (64)Cu-N-NE3TA-Tf was shown to have rapid blood clearance and increasing tumor uptake in PC-3 tumor bearing mice over a 24h period. This bifunctional chelate presents highly efficient chelation chemistry with (64)Cu under mild condition that can be applied for radiolabeling of various tumor-specific biomolecules with (64)Cu for potential use in PET imaging applications.
authors.affiliation: Department of Biological and Chemical Sciences, Illinois Institute of Technology, Chicago, IL, United States.
authors.forename: Chi Soo
authors.initials: CS
authors.lastname: Kang
authors.affiliation: Department of Biological and Chemical Sciences, Illinois Institute of Technology, Chicago, IL, United States.
authors.forename: Ningjie
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Biological and Chemical Sciences, Illinois Institute of Technology, Chicago, IL, United States.
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biological and Chemical Sciences, Illinois Institute of Technology, Chicago, IL, United States.
authors.forename: Xiang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, United States.
authors.forename: Nilantha
authors.initials: N
authors.lastname: Bandara
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, United States.
authors.forename: Dijie
authors.initials: D
authors.lastname: Liu
authors.affiliation: Research Service, Harry S. Truman Memorial Veterans' Hospital, United States; Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lewis
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, United States.
authors.forename: Buck E
authors.initials: BE
authors.lastname: Rogers
authors.affiliation: Department of Biological and Chemical Sciences, Illinois Institute of Technology, Chicago, IL, United States. Electronic address: Chong@iit.edu.
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Chong
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D003301:Copper Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D005260:Female; D006207:Half-Life; D008297:Male; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010880:Piperidines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014168:Transferrin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
chemical_list: D001372:Aza Compounds; D002614:Chelating Agents; D003301:Copper Radioisotopes; D010880:Piperidines; D019275:Radiopharmaceuticals; D014168:Transferrin; C482777:triazacyclononane
keywords: Bifunctional chelator; Biodistribution; Copper 64; Radiolabeling; Serum stability; Transferrin