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This article is part of the supplement: 18th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

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A PET microdosing study with the P-glycoprotein inhibitor tariquidar

Martin Bauer1, Markus Zeitlinger1, Cécile Philippe2, Johann Stanek13, Wolfgang Wadsak2, Markus Mitterhauser2, Georgios Karanikas2, Markus Müller1 and Oliver Langer13*

Author Affiliations

1 Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria

2 Department of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria

3 Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444 Seibersdorf, Austria

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BMC Pharmacology and Toxicology 2012, 13(Suppl 1):A17  doi:10.1186/2050-6511-13-S1-A17

The electronic version of this article is the complete one and can be found online at:

Published:17 September 2012

© 2012 Bauer et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The adenosine triphosphate-binding cassette transporters P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) restrict absorption and body distribution and promote excretion of several clinically used drugs. Tariquidar (XR9576) is a potent third-generation dual Pgp and BCRP inhibitor, which is currently tested in clinical trials to overcome chemoresistance of tumors and to enhance brain distribution of Pgp/BCRP substrate drugs. We performed a positron emission tomography (PET) microdosing study with carbon-11-labelled tariquidar ([11C]tariquidar) which aimed at assessing the brain distribution of [11C]tariquidar in healthy volunteers.


Six healthy subjects received an i.v. bolus injection of approximately 400 MBq of [11C]tariquidar containing less than 30 µg of unlabelled tariquidar. Then, dynamic brain PET scans and arterial blood sampling were performed. Radiolabelled metabolites of [11C]tariquidar in plasma were measured with a solid-phase extraction/HPLC assay. Brain activity uptake was expressed as the ratio of the area under the whole brain grey matter time-activity curve to the area under the plasma time-activity curve from time 0 to 60 min (AUC0–60 brain/AUC0–60 plasma).


Brain activity uptake was low after injection of [11C]tariquidar with a mean AUC0–60 brain/AUC0–60 plasma of 0.14 ± 0.03. At 60 min after radiotracer injection, 78 ± 12% of total radioactivity in plasma was in the form of unchanged parent radiotracer. Less than 1% of the total injected dose excreted in urine over 90 min.


Low brain uptake of radioactivity is consistent with tariquidar being, at microdoses, a dual substrate of Pgp and BCRP. [11C]Tariquidar PET after inhibition of Pgp with unlabelled tariquidar may be a promising approach to selectively assess BCRP function at the human blood-brain barrier.


Funded by the European Community’s Seventh Framework Program (grant agreement 201380 (Euripides)) and Austrian Science Fund (FWF) project ”Transmembrane Transporters in Health and Disease” (SFB F35).