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A PET microdosing study with the P-glycoprotein inhibitor tariquidar


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).

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Correspondence to Oliver Langer.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is 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.

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Bauer, M., Zeitlinger, M., Philippe, C. et al. A PET microdosing study with the P-glycoprotein inhibitor tariquidar. BMC Pharmacol Toxicol 13 (Suppl 1), A17 (2012).

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