title: Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of [(11)C]CO2.
abstract: Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [(11)C]CO2 followed by an intermolecular cycloaddition between a [(11)C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [(11)C]ibrutinib (Bruton's tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [(11)C]acrylic acid (generated from [(11)C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully automated on commercial radiochemical synthesis modules and provide radiotracers in 1-5% radiochemical yield (noncorrected, based upon [(11)C]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Mossine
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.
authors.forename: Allen F
authors.initials: AF
authors.lastname: Brooks
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Jackson
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Quesada
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.
authors.forename: Phillip
authors.initials: P
authors.lastname: Sherman
authors.affiliation: Discovery Chemistry Platforms, PET Radiochemical Synthesis, Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08648, United States.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Cole
authors.affiliation: Discovery Chemistry Platforms, PET Radiochemical Synthesis, Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08648, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Donnelly
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.|The Interdepartmental Program in Medicinal Chemistry, The University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Scott
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.
authors.forename: Xia
authors.initials: X
authors.lastname: Shao
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000138:chemical synthesis* / Q000737:chemistry*; D002250:Carbon Radioisotopes; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D051379:Mice; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D051381:Rats
chemical_list: D002250:Carbon Radioisotopes; D011849:Radioactive Tracers; D002245:Carbon Dioxide