{"@context":{"aiiso":"http:\/\/purl.org\/vocab\/aiiso\/schema#","arm":"https:\/\/ld4p.github.io\/arm\/core\/ontology\/0.1\/","bf":"http:\/\/id.loc.gov\/ontologies\/bibframe\/","bib":"https:\/\/bibliotek-o.org\/","bibo":"http:\/\/purl.org\/ontology\/bibo\/","cito":"http:\/\/purl.org\/spar\/cito\/","classSchemes":"http:\/\/id.loc.gov\/vocabulary\/classSchemes","dbo":"http:\/\/dbpedia.org\/ontology\/","dce":"http:\/\/purl.org\/dc\/elements\/1.1\/","dcmitype":"http:\/\/dublincore.org\/documents\/2000\/07\/11\/dcmi-type-vocabulary\/#","dcterms":"http:\/\/purl.org\/dc\/terms\/","ebucore":"http:\/\/www.ebu.ch\/metadata\/ontologies\/ebucore\/ebucore","edm":"http:\/\/www.europeana.eu\/schemas\/edm\/","foaf":"http:\/\/xmlns.com\/foaf\/spec\/#","frap":"http:\/\/purl.org\/cerif\/frapo","identifiers":"http:\/\/id.loc.gov\/vocabulary\/identifiers","ids":"http:\/\/id.loc.gov\/vocabulary\/identifiers\/","opaque":"http:\/\/opaquenamespace.org\/","pcdm":"http:\/\/pcdm.org\/models#","phaidra":"https:\/\/phaidra.org\/ontology\/","rdam":"http:\/\/rdaregistry.info\/Elements\/m\/","rdau":"http:\/\/rdaregistry.info\/Elements\/u\/","rdax":"http:\/\/rdaregistry.info\/Elements\/x\/","rdf":"http:\/\/www.w3.org\/1999\/02\/22-rdf-syntax-ns#","rdfs":"https:\/\/www.w3.org\/TR\/rdf-schema\/","relators":"http:\/\/id.loc.gov\/vocabulary\/relators","role":{"@context":{"aut":{"@container":"@list","@id":"http:\/\/id.loc.gov\/vocabulary\/relators\/aut"}}},"schema":"http:\/\/schema.org\/","skos":"http:\/\/www.w3.org\/2004\/02\/skos\/core#","skosxl":"http:\/\/www.w3.org\/2008\/05\/skos-xl"},"@id":"https:\/\/phaidra.vetmeduni.ac.at\/o:4452","bf:note":[{"@type":"bf:Summary","skos:prefLabel":[{"@language":"eng","@value":"The efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier limits the cerebral uptake of various xenobiotics. To assess the sensitivity of [11C]metoclopramide to measure decreased cerebral P-gp function, we performed [11C]metoclopramide PET scans without (baseline) and with partial P-gp inhibition by tariquidar in wild-type, heterozygous Abcb1a\/b(+\/−) and homozygous Abcb1a\/b(−\/−) mice as models with controlled levels of cerebral P-gp expression. Brains were collected to quantify P-gp expression with immunohistochemistry. Brain uptake of [11C]metoclopramide was expressed as the area under the brain time-activity curve (AUCbrain) and compared with data previously obtained with (R)-[11C]verapamil and [11C]N-desmethyl-loperamide. Abcb1a\/b(+\/−) mice had intermediate P-gp expression compared to wild-type and Abcb1a\/b(−\/−) mice. In baseline scans, all three radiotracers were able to discriminate Abcb1a\/b(−\/−) from wild-type mice (2.5- to 4.6-fold increased AUCbrain, p ≤ 0.0001). However, only [11C]metoclopramide could discriminate Abcb1a\/b(+\/−) from wild-type mice (1.46-fold increased AUCbrain, p ≤ 0.001). After partial P-gp inhibition, differences in [11C]metoclopramide AUCbrain between Abcb1a\/b(+\/−) and wild-type mice (1.39-fold, p ≤ 0.001) remained comparable to baseline. There was a negative correlation between baseline [11C]metoclopramide AUCbrain and ex-vivo-measured P-gp immunofluorescence (r = −0.9875, p ≤ 0.0001). Our data suggest that [11C]metoclopramide is a sensitive radiotracer to measure moderate, but (patho-)physiologically relevant decreases in cerebral P-gp function without the need to co-administer a P-gp inhibitor."}]}],"bf:provisionActivity":[{"@type":"bf:Publication","bf:agent":[{"@type":"schema:Organization","schema:name":[{"@value":"Sage"}]}]}],"dce:rights":[{"@language":"eng","@value":"Copyright © 2024"}],"dce:subject":[{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"P-Glycoprotein"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Blood-Brain Barrier"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"PET"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"[11C]metoclopramide"}]},{"@type":"skos:Concept","skos:prefLabel":[{"@language":"eng","@value":"Heterozygous Abcb1a\/b Knockout Mice"}]}],"dce:title":[{"@type":"bf:Title","bf:mainTitle":[{"@language":"eng","@value":"[11C]metoclopramide is a sensitive radiotracer to measure moderate decreases in P-glycoprotein function at the blood-brain barrier"}]}],"dcterms:accessRights":[{"@type":"skos:Concept","skos:exactMatch":["https:\/\/pid.phaidra.org\/vocabulary\/QW5R-NG4J"],"skos:prefLabel":[{"@language":"eng","@value":"open access"}]}],"dcterms:issued":["2024"],"dcterms:language":["eng"],"dcterms:type":[{"@type":"skos:Concept","skos:exactMatch":["https:\/\/pid.phaidra.org\/vocabulary\/69ZZ-2KGX"],"skos:prefLabel":[{"@language":"eng","@value":"Text"},{"@language":"deu","@value":"Text"},{"@language":"ita","@value":"Testo"}]}],"ebucore:filename":["mairinger-et-al-2023-11c-metoclopramide-is-a-sensitive-radiotracer-to-measure-moderate-decreases-in-p-glycoprotein.pdf"],"ebucore:hasMimeType":["application\/pdf"],"edm:hasType":[{"@type":"skos:Concept","skos:exactMatch":["https:\/\/pid.phaidra.org\/vocabulary\/VKA6-9XTY"],"skos:prefLabel":[{"@language":"eng","@value":"journal article"},{"@language":"deu","@value":"Wissenschaftlicher Artikel"},{"@language":"ita","@value":"Articolo di rivista"}]}],"edm:rights":["http:\/\/creativecommons.org\/licenses\/by\/4.0\/"],"oaire:version":[{"@type":"skos:Concept","skos:exactMatch":["https:\/\/pid.phaidra.org\/vocabulary\/PMR8-3C8D"],"skos:prefLabel":[{"@language":"eng","@value":"version of record (published version)"}]}],"rdam:P30004":[{"@type":"ids:doi","@value":"10.1177\/0271678X231202336"}],"rdau:P60193":[{"@type":"schema:CreativeWork","bibo:issue":["1"],"bibo:volume":["44"],"dce:title":[{"@type":"bf:Title","bf:mainTitle":[{"@language":"eng","@value":"Journal Of Cerebral Blood Flow And Metabolism"}]}],"dcterms:issued":["2024"],"ids:issn":["1559-7016"]}],"role:aut":[{"@type":"schema:Person","schema:familyName":[{"@value":"Mairinger"}],"schema:givenName":[{"@value":"Severin"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Leterrier"}],"schema:givenName":[{"@value":"S."}]},{"@type":"schema:Person","schema:affiliation":[{"@type":"schema:Organization","schema:name":[{"@value":"University of Veterinary Medicine Vienna"}],"skos:exactMatch":["https:\/\/ror.org\/01w6qp003"]}],"schema:familyName":[{"@value":"Filip"}],"schema:givenName":[{"@value":"Thomas"}],"skos:exactMatch":[{"@type":"ids:orcid","@value":"0009-0006-9169-6032"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Loebsch"}],"schema:givenName":[{"@value":"Mathilde"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Pahnke"}],"schema:givenName":[{"@value":"Jens"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Hernández-Lozano"}],"schema:givenName":[{"@value":"Irene"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Stanek"}],"schema:givenName":[{"@value":"J."}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Tournier"}],"schema:givenName":[{"@value":"Nicolas"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Zeitlinger"}],"schema:givenName":[{"@value":"Markus"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Hacker"}],"schema:givenName":[{"@value":"Marcus"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Langer"}],"schema:givenName":[{"@value":"Oliver"}]},{"@type":"schema:Person","schema:familyName":[{"@value":"Wanek"}],"schema:givenName":[{"@value":"Thomas"}]}],"schema:numberOfPages":["11"]}