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dc.contributor.authorMcGinnity, Colm J
dc.contributor.authorÅrstad, Erik
dc.contributor.authorBeck, Katherine
dc.contributor.authorBrooks, David J
dc.contributor.authorColes, Jonathan
dc.contributor.authorDuncan, John S
dc.contributor.authorGalovic, Marian
dc.contributor.authorHinz, Rainer
dc.contributor.authorHirani, Ella
dc.contributor.authorHowes, Oliver D
dc.contributor.authorJones, Paul A
dc.contributor.authorKoepp, Matthias J
dc.contributor.authorLuo, Feng
dc.contributor.authorRiaño Barros, Daniela A
dc.contributor.authorSingh, Nisha
dc.contributor.authorTrigg, William
dc.contributor.authorHammers, Alexander
dc.date.accessioned2018-10-03T04:44:29Z
dc.date.available2018-10-03T04:44:29Z
dc.date.issued2019-01-16
dc.identifier.issn1948-7193
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283060
dc.description.abstractSchoenberger and colleagues ( Schoenberger et al. ( 2018 ) ACS Chem. Neurosci. 9 , 298 - 305 ) recently reported attempts to demonstrate specific binding of the positron emission tomography (PET) radiotracer, [18F]GE-179, to NMDA receptors in both rats and Rhesus macaques. GE-179 did not work as expected in animal models; however, we disagree with the authors' conclusion that "the [18F]GE-179 signal seems to be largely nonspecific". It is extremely challenging to demonstrate specific binding for the use-dependent NMDA receptor intrachannel ligands such as [18F]GE-179 in animals via traditional blocking, due to its low availability of target sites ( Bmax'). Schoenberger and colleagues anesthetized rats and Rhesus monkeys using isoflurane, which has an inhibitory effect on NMDA receptor function and thus would be expected to further reduce the Bmax'. The extent of glutamate release achieved in the provocation experiments is uncertain, as is whether a significant increase in NMDA receptor channel opening can be expected under anesthesia. Prior data suggest that the uptake of disubstituted arylguanidine-based ligands such as GE-179 can be reduced by phencyclidine binding site antagonists, if injection is performed in the absence of ketamine and isoflurane anesthesia, e.g., with GE-179's antecedent, CNS 5161 ( Biegon et al. ( 2007 ) Synapse 61 , 577 - 586 ), and with GMOM ( van der Doef et al. ( 2016 ) J. Cereb. Blood Flow Metab. 36 , 1111 - 1121 ). However, the extent of nonspecific uptake remains uncertain.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Chemical Society (ACS)
dc.subjectBrain
dc.subjectAnimals
dc.subjectMacaca mulatta
dc.subjectRodentia
dc.subjectRats
dc.subjectN-Methylaspartate
dc.subjectRadiopharmaceuticals
dc.subjectPositron-Emission Tomography
dc.titleComment on " In Vivo [18F]GE-179 Brain Signal Does Not Show NMDA-Specific Modulation with Drug Challenges in Rodents and Nonhuman Primates".
dc.typeArticle
prism.endingPage772
prism.issueIdentifier1
prism.publicationDate2019
prism.publicationNameACS Chem Neurosci
prism.startingPage768
prism.volume10
dc.identifier.doi10.17863/CAM.30422
dcterms.dateAccepted2018-07-18
rioxxterms.versionofrecord10.1021/acschemneuro.8b00246
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-01
dc.contributor.orcidMcGinnity, Colm J [0000-0002-2692-918X]
dc.contributor.orcidÅrstad, Erik [0000-0002-3240-2106]
dc.contributor.orcidColes, Jonathan [0000-0003-4013-679X]
dc.identifier.eissn1948-7193
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/K02308X/1)
pubs.funder-project-idMedical Research Council (MR/L013215/1)
cam.issuedOnline2018-10-11
rioxxterms.freetoread.startdate2019-10-11


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