Preclinical PET Neuroimaging of [11C]Bexarotene

Benjamin H Rotstein; Michael S Placzek; Hema S Krishnan; Aleksandra Pekošak; Thomas Lee Collier; Changning Wang; Steven H Liang; Ethan S Burstein; Jacob M Hooker; Neil Vasdev

doi:10.1177/1536012116663054

Preclinical PET Neuroimaging of [11C]Bexarotene

Mol Imaging. 2016 Aug 23:15:1536012116663054. doi: 10.1177/1536012116663054. Print 2016.

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ Department of Radiology, Harvard Medical School, Boston, MA, USA Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
⁶ ACADIA Pharmaceuticals, Inc, San Diego, CA, USA.

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.

Keywords: bexarotene; carbon-11; neuroimaging; positron emission tomography; retinoid X receptor.

MeSH terms

Animals
Bexarotene
Brain / diagnostic imaging*
Brain / metabolism
Carbon Radioisotopes / chemistry
Male
Neuroimaging / methods*
Positron-Emission Tomography
Primates
Radiopharmaceuticals / chemistry
Rats
Retinoid X Receptors / agonists
Retinoid X Receptors / metabolism
Tetrahydronaphthalenes / chemistry
Tetrahydronaphthalenes / pharmacology*

Substances

Carbon Radioisotopes
Radiopharmaceuticals
Retinoid X Receptors
Tetrahydronaphthalenes
Bexarotene

Preclinical PET Neuroimaging of [11C]Bexarotene

Authors

Affiliations

Abstract

MeSH terms

Substances

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