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[11C]Flumazenil bra...
[11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein.
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Froklage, Femke E (författare)
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- Syvänen, Stina (författare)
- Leiden University
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Hendrikse, N Harry (författare)
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Huisman, Marc C (författare)
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Molthoff, Carla Fm (författare)
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Tagawa, Yoshihiko (författare)
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Reijneveld, Jaap C (författare)
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Heimans, Jan J (författare)
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Lammertsma, Adriaan A (författare)
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- Eriksson, Jonas (författare)
- VU University Medical Center Amsterdam
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de Lange, Elizabeth Cm (författare)
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Voskuyl, Rob A (författare)
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(creator_code:org_t)
- 2012
- 2012
- Engelska.
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Ingår i: EJNMMI Research. - 2191-219X. ; 2, s. 12-
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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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.
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Froklage, Femke ...
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Syvänen, Stina
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Hendrikse, N Har ...
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Huisman, Marc C
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Molthoff, Carla ...
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Tagawa, Yoshihik ...
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visa fler...
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Reijneveld, Jaap ...
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Heimans, Jan J
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Lammertsma, Adri ...
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Eriksson, Jonas
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de Lange, Elizab ...
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Voskuyl, Rob A
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Uppsala universitet