Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier

• Published in: Journal of cerebral blood flow and metabolism Vol. 30; no. 3; pp. 510 - 515
• Main Authors: Bauer, Martin, Karch, Rudolf, Neumann, Friederike, Wagner, Claudia C, Kletter, Kurt, Müller, Markus, Löscher, Wolfgang, Zeitlinger, Markus, Langer, Oliver
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-03-2010; Nature Publishing Group; Sage Publications Ltd
• Subjects: Adult; ATP-Binding Cassette, Sub-Family B, Member 1 - physiology; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiology; Brain - diagnostic imaging; Brief Communication; Calcium Channel Blockers - metabolism; Drug Resistance, Multiple - drug effects; Epilepsy - chemically induced; Epilepsy - physiopathology; Humans; Image Processing, Computer-Assisted; Infusions, Intravenous; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Nervous system; Neurology; Positron-Emission Tomography; Quinolines - pharmacology; Ultrasonic investigative techniques; Vascular diseases and vascular malformations of the nervous system; Verapamil - metabolism; P-glycoprotein; blood–brain barrier; tariquidar; positron emission tomography (PET); regional; (R)-[11C]verapamil; Antineoplastic agent; Human; blood-brain barrier; Nervous system diseases; regional tariquidar; Tariquidar; Calcium antagonist; Glycoprotein; C]verapamil; Antiarrhythmic agent; Blood brain barrier; Cerebral disorder; Central nervous system disease; Aralkylamine; Verapamil; Positron emission tomography; (R)-; Cerebrovascular disease; Emission tomography
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2009.265

We attempted to assess regional differences in cerebral P-glycoprotein (P-gp) function by performing paired positron emission tomography (PET) scans with the P-gp substrate (R)-[11C]verapamil in five healthy subjects before and after i.v. infusion of tariquidar (2 mg/kg). Comparison of tariquidar-induced changes in distribution volumes (DVs) in 42 brain regions of interest (ROIs) failed to detect significant differences among brain ROIs. Statistical parametric mapping analysis of parametric DV images visualized symmetrical bilateral clusters with moderately higher DV increases in response to tariquidar administration in cerebellum, parahippocampal gyrus, olfactory gyrus, and middle temporal lobe and cortex, which might reflect moderately decreased P-gp function and expression.