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Sökning: WFRF:(Syvänen A C) > [11C]Flumazenil bra...

  • Froklage, Femke E (författare)

[11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein.

  • Artikel/kapitelEngelska2012

Förlag, utgivningsår, omfång ...

  • 2012
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-185288
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-185288URI
  • https://doi.org/10.1186/2191-219X-2-12DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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.

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Syvänen, StinaLeiden University(Swepub:uu)stsyv838 (författare)
  • Hendrikse, N Harry (författare)
  • Huisman, Marc C (författare)
  • Molthoff, Carla Fm (författare)
  • Tagawa, Yoshihiko (författare)
  • Reijneveld, Jaap C (författare)
  • Heimans, Jan J (författare)
  • Lammertsma, Adriaan A (författare)
  • Eriksson, JonasVU University Medical Center Amsterdam(Swepub:uu)joeri542 (författare)
  • de Lange, Elizabeth Cm (författare)
  • Voskuyl, Rob A (författare)
  • Leiden UniversityVU University Medical Center Amsterdam (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:EJNMMI Research2, s. 12-2191-219X

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