title: A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil from [18F]Fluoride for Human PET Imaging.
abstract: Translation of new18F-fluorination reactions to produce radiotracers for human positron emission tomography (PET) imaging is rare because the chemistry must have useful scope and the process for18F-labeled tracer production must be robust and simple to execute. The application of transition metal mediators has enabled impactful18F-fluorination methods, but to date none of these reactions have been applied to produce a human-injectable PET tracer. In this article we present chemistry and process innovations that culminate in the first production from [18F]fluoride of human doses of [18F]5-fluorouracil, a PET tracer for cancer imaging in humans. The first preparation of nickel σ-aryl complexes by transmetalation from arylboronic acids or esters was developed and enabled the synthesis of the [18F]5-fluorouracil precursor. Routine production of >10 mCi doses of [18F]5-fluorouracil was accomplished with a new instrument for azeotrope-free [18F]fluoride concentration in a process that leverages the tolerance of water in nickel-mediated18F-fluorination.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hoover
authors.affiliation: Department of Molecular and Medical Pharmacology and Crump Institute for Molecular Imaging, David Geffen School of Medicine at University of California, Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Lazari
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, United States; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Molecular and Medical Pharmacology and Crump Institute for Molecular Imaging, David Geffen School of Medicine at University of California, Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
authors.forename: Maruthi Kumar
authors.initials: MK
authors.lastname: Narayanam
authors.affiliation: Department of Molecular and Medical Pharmacology and Crump Institute for Molecular Imaging, David Geffen School of Medicine at University of California, Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Murphy
authors.affiliation: Department of Molecular and Medical Pharmacology and Crump Institute for Molecular Imaging, David Geffen School of Medicine at University of California, Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
authors.forename: R Michael
authors.initials: RM
authors.lastname: van Dam
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, United States; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ritter