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[11C]Flumazenil bra...
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Froklage, Femke E
(author)
[11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein.
- Article/chapterEnglish2012
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LIBRIS-ID:oai:DiVA.org:uu-185288
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-185288URI
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https://doi.org/10.1186/2191-219X-2-12DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Added entries (persons, corporate bodies, meetings, titles ...)
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Syvänen, StinaLeiden University(Swepub:uu)stsyv838
(author)
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Hendrikse, N Harry
(author)
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Huisman, Marc C
(author)
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Molthoff, Carla Fm
(author)
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Tagawa, Yoshihiko
(author)
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Reijneveld, Jaap C
(author)
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Heimans, Jan J
(author)
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Lammertsma, Adriaan A
(author)
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Eriksson, JonasVU University Medical Center Amsterdam(Swepub:uu)joeri542
(author)
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de Lange, Elizabeth Cm
(author)
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Voskuyl, Rob A
(author)
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Leiden UniversityVU University Medical Center Amsterdam
(creator_code:org_t)
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In:EJNMMI Research2, s. 12-2191-219X
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Uppsala University