18 F]FSPG-PET reveals increased cystine/glutamate antiporter (xc-) activity in a mouse model of multiple sclerosis

Journal of Neuroinflammation
Aileen HoehneSanjiv S Gambhir

Abstract

The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18F]fluoropropyl)-L-glutamate ([18F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55) peptide in complete Freund's adjuvant (CFA) followed by pertussis toxin. Control mice received CFA emulsion and pertussis toxin without MOG peptide, while a separate cohort of naïve mice received no treatment. PET studies were performed to investigate the kinetics and distribution of [18F]FSPG in naïve, control, pre-symptomatic, and symptomatic EAE mice, compared to 18F-fluorodeoxyglucose ([18F]FDG). After final PET scans, each mouse was perfused and radioactivity in dissected tissues was measured using a gamma counter. Central nervous system (CNS) tissues were further analyzed using ex vivo autoradiography or western blot. [18F]FSPG uptake ...Continue Reading

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Citations

Sep 22, 2018·Chembiochem : a European Journal of Chemical Biology·Hye Jin LeeWeibo Cai
Nov 8, 2019·Journal of Labelled Compounds & Radiopharmaceuticals·Santosh R AlluriPatrick J Riss
Aug 14, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Daniel KrysFrank Wuest
Oct 30, 2019·EJNMMI Radiopharmacy and Chemistry·Matteo BaucknehtSilvia Morbelli
Sep 20, 2020·Journal of Neuroinflammation·Marc Y StevensMichelle L James
Jul 23, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sonya Youngju ParkErik S Mittra
Oct 4, 2019·Bioorganic Chemistry·Tamar GetterArie Gruzman
Jun 7, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Corinne BeinatSanjiv Sam Gambhir

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Methods Mentioned

BETA
protein assay
imaging technique

Software Mentioned

VivoQuant
ImageJ
FASTMAP
GraphPad

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