title: Synthesis of [(11)C]Bexarotene by Cu-Mediated [(11)C]Carbon Dioxide Fixation and Preliminary PET Imaging.
abstract: Bexarotene (Targretin) is a retinoid X receptor (RXR) agonist that has applications for treatment of T cell lymphoma and proposed mechanisms of action in Alzheimer's disease that have been the subject of recent controversy. Carbon-11 labeled bexarotene ([(11)C-carbonyl]4-[1-(3,5,5,8,8-pentamethyltetralin-2-yl)ethenyl]benzoic acid) was synthesized using a Cu-mediated cross-coupling reaction employing an arylboronate precursor 1 and [(11)C]carbon dioxide under atmospheric pressure in 15 ± 2% uncorrected radiochemical yield (n = 3), based on [(11)C]CO2. Judicious choice of solvents, catalysts, and additives, as well as precursor concentration and purity of [(11)C]CO2, enabled the preparation of this (11)C-labeled carboxylic acid. Formulated [(11)C]bexarotene was isolated (>37 mCi) with >99% radiochemical purity in 32 min. Preliminary positron emission tomography-magnetic resonance imaging revealed rapid brain uptake in nonhuman primate in the first 75 s following intravenous administration of the radiotracer (specific activity >0.3 Ci/μmol at time of injection), followed by slow clearance (Δ = -43%) over 60 min. Modest uptake (SUVmax = 0.8) was observed in whole brain and regions with high RXR expression.
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital , Boston, Massachusetts 02114, United States ; Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Rotstein
authors.affiliation: Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States ; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital , Boston, Massachusetts 02114, United States.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Woo
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital , Boston, Massachusetts 02114, United States ; Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States ; Advion, Inc. , Ithaca, New York 14850, United States.
authors.forename: Thomas Lee
authors.initials: TL
authors.lastname: Collier
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital , Boston, Massachusetts 02114, United States ; Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Brady
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital , Boston, Massachusetts 02114, United States ; Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Liang
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging & Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital , Boston, Massachusetts 02114, United States ; Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States.
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
keywords: Alzheimer’s disease; Bexarotene; carbon dioxide fixation; carbon-11; positron emission tomography; retinoid X receptor; targretin