title: Preclinical PET Neuroimaging of [11C]Bexarotene.
abstract: Activation of retinoid X receptors (RXRs) has been proposed as a therapeutic mechanism for the treatment of neurodegeneration, including Alzheimer's and Parkinson's diseases. We previously reported radiolabeling of a Food and Drug Administration-approved RXR agonist, bexarotene, by copper-mediated [(11)C]CO2 fixation and preliminary positron emission tomography (PET) neuroimaging that demonstrated brain permeability in nonhuman primate with regional binding distribution consistent with RXRs. In this study, the brain uptake and saturability of [(11)C]bexarotene were studied in rats and nonhuman primates by PET imaging under baseline and greater target occupancy conditions. [(11)C]Bexarotene displays a high proportion of nonsaturable uptake in the brain and is unsuitable for RXR occupancy measurements in the central nervous system.
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Gordon Center for Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA Department of Radiology, Harvard Medical School, Boston, MA, USA vasdev.neil@mgh.harvard.edu benjamin.rotstein@uottawa.ca.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Rotstein
authors.affiliation: Department of Radiology, Harvard Medical School, Boston, MA, USA Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA Department of Psychiatry, McLean Imaging Center, McLean Hospital, Belmont, MA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Placzek
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Gordon Center for Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Hema S
authors.initials: HS
authors.lastname: Krishnan
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Gordon Center for Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pekošak
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Gordon Center for Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA Department of Radiology, Harvard Medical School, Boston, MA, USA Advion, Inc, Ithaca, NY, USA.
authors.forename: Thomas Lee
authors.initials: TL
authors.lastname: Collier
authors.affiliation: Department of Radiology, Harvard Medical School, Boston, MA, USA Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Changning
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Gordon Center for Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Liang
authors.affiliation: ACADIA Pharmaceuticals, Inc, San Diego, CA, USA.
authors.forename: Ethan S
authors.initials: ES
authors.lastname: Burstein
authors.affiliation: Department of Radiology, Harvard Medical School, Boston, MA, USA Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Gordon Center for Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA Department of Radiology, Harvard Medical School, Boston, MA, USA vasdev.neil@mgh.harvard.edu benjamin.rotstein@uottawa.ca.
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
mesh_terms: D000818:Animals; D000077610:Bexarotene; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry; D008297:Male; D059906:Neuroimaging / Q000379:methods*; D049268:Positron-Emission Tomography; D011323:Primates; D019275:Radiopharmaceuticals / Q000737:chemistry; D051381:Rats; D047488:Retinoid X Receptors / Q000819:agonists / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene
keywords: bexarotene; carbon-11; neuroimaging; positron emission tomography; retinoid X receptor