Abstract
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 language | English |
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Pages (from-to) | 97-105 |
Number of pages | 9 |
Journal | Journal of cerebral blood flow and metabolism |
Volume | 37 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2017 |
Keywords
- Blood-brain barrier
- P-glycoprotein
- flumazenil
- positron emission tomography
- temporal lobe epilepsy