Altered GABA A receptor density and unaltered blood-brain barrier [11C]flumazenil transport in drug-resistant epilepsy patients with mesial temporal sclerosis

Femke E. Froklage*, Andrey Postnov, Maqsood M. Yaqub, Esther Bakker, Ronald Boellaard, N. Harry Hendrikse, Emile F.I. Comans, Robert C. Schuit, Patrick Schober, Demetrios N. Velis, Jack Zwemmer, Jan J. Heimans, Adriaan A. Lammertsma, Rob A. Voskuyl, Jaap C. Reijneveld

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Studies in rodents suggest that flumazenil is a P-glycoprotein substrate at the blood-brain barrier. This study aimed to assess whether [11C]flumazenil is a P-glycoprotein substrate in humans and to what extent increased P-glycoprotein function in epilepsy may confound interpretation of clinical [11C]flumazenil studies used to assess gamma-aminobutyric acid A receptors. Nine drug-resistant patients with epilepsy and mesial temporal sclerosis were scanned twice using [11C]flumazenil before and after partial P-glycoprotein blockade with tariquidar. Volume of distribution, nondisplaceable binding potential, and the ratio of rate constants of [11C]flumazenil transport across the blood-brain barrier (K 1/k 2) were derived for whole brain and several regions. All parameters were compared between pre-and post-tariquidar scans. Regional results were compared between mesial temporal sclerosis and contralateral sides. Tariquidar significantly increased global K 1/k 2 (+23%) and volume of distribution (+10%), but not nondisplaceable binding potential. At the mesial temporal sclerosis side volume of distribution and nondisplaceable binding potential were lower in hippocampus (both â '1/4-19%) and amygdala (both â '1/4-16%), but K 1/k 2 did not differ, suggesting that only regional gamma-aminobutyric acid A receptor density is altered in epilepsy. In conclusion, although [11C]flumazenil appears to be a (weak) P-glycoprotein substrate in humans, this does not seem to affect its role as a tracer for assessing gamma-aminobutyric acid A receptor density.

Original languageEnglish
Pages (from-to)97-105
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number1
Publication statusPublished - 1 Jan 2017

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