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Sökning: WFRF:(Huisman Marc C) > [11C]Flumazenil bra...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003277naa a2200385 4500
001oai:DiVA.org:uu-185288
003SwePub
008121121s2012 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1852882 URI
0247 a https://doi.org/10.1186/2191-219X-2-122 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Froklage, Femke E4 aut
2451 0a [11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein.
264 1c 2012
338 a print2 rdacarrier
520 a BACKGROUND: [11C]Flumazenil and positron emission tomography (PET) are used clinically to assess gamma-aminobutyric acid (GABA)-ergic function and to localize epileptic foci prior to resective surgery. Enhanced P-glycoprotein (P-gp) activity has been reported in epilepsy and this may confound interpretation of clinical scans if [11C]flumazenil is a P-gp substrate. The purpose of this study was to investigate whether [11C]flumazenil is a P-gp substrate.METHODS: [11C]Flumazenil PET scans were performed in wild type (WT) (n = 9) and Mdr1a/1b, (the genes that encode for P-gp) double knockout (dKO) (n = 10) mice, and in naive rats (n = 10). In parallel to PET scanning, [11C]flumazenil plasma concentrations were measured in rats. For 6 of the WT and 6 of the dKO mice a second, [11C]flumazenil scan was acquired after administration of the P-gp inhibitor tariquidar. Cerebral [11C]flumazenil concentrations in WT and Mdr1a/1b dKO mice were compared (genetic disruption model). Furthermore, pre and post P-gp-blocking cerebral [11C]flumazenil concentrations were compared in all animals (pharmacological inhibition model).RESULTS: Mdr1a/1b dKO mice had approximately 70% higher [11C]flumazenil uptake in the brain than WT mice. After administration of tariquidar, cerebral [11C]flumazenil uptake in WT mice increased by about 80% in WT mice, while it remained the same in Mdr1a/1b dKO mice. In rats, cerebral [11C]flumazenil uptake increased by about 60% after tariquidar administration. Tariquidar had only a small effect on plasma clearance of flumazenil.CONCLUSIONS: The present study showed that [11C]flumazenil is a P-gp substrate in rodents. Consequently, altered cerebral [11C]flumazenil uptake, as observed in epilepsy, may not reflect solely GABAA receptor density changes but also changes in P-gp activity.
7001 a Syvänen, Stinau Leiden University4 aut0 (Swepub:uu)stsyv838
7001 a Hendrikse, N Harry4 aut
7001 a Huisman, Marc C4 aut
7001 a Molthoff, Carla Fm4 aut
7001 a Tagawa, Yoshihiko4 aut
7001 a Reijneveld, Jaap C4 aut
7001 a Heimans, Jan J4 aut
7001 a Lammertsma, Adriaan A4 aut
7001 a Eriksson, Jonasu VU University Medical Center Amsterdam4 aut0 (Swepub:uu)joeri542
7001 a de Lange, Elizabeth Cm4 aut
7001 a Voskuyl, Rob A4 aut
7102 a Leiden Universityb VU University Medical Center Amsterdam4 org
7730 t EJNMMI Researchg 2, s. 12-q 2<12-x 2191-219X
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-185288
8564 8u https://doi.org/10.1186/2191-219X-2-12

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