Abstract
Background The ATP-binding cassette (ABC) transporters breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) are expressed in the blood-brain barrier (BBB), where they impede brain uptake of their substrates by active efflux transport. BCRP has recently been shown to be the quantitatively most important ABC transporter at the human BBB. Inhibition of BCRP by inhibitors such as the fumitremorgin C derivative Ko143 [1] may be an interesting strategy to improve brain uptake of BCRP substrates. The aim of this study was to assess the dose-response relationship of Ko143 for inhibition of Bcrp1 at the murine BBB using small-animal positron emission tomography (PET) together with the dual P-gp/BCRP substrate radiotracer [C]tariquidar.
Highlights
Open AccessInhibition of breast cancer resistance protein at the murine blood-brain barrier by Ko143 studied with [11C]tariquidar and positron emission tomography (PET)
The ATP-binding cassette (ABC) transporters breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) are expressed in the blood-brain barrier (BBB), where they impede brain uptake of their substrates by active efflux transport
Methods [11C]Tariquidar positron emission tomography (PET) scans were performed in female wild-type (FVB), Bcrp1−/− and Mdr1a/b−/− mice before and 60 min after i.v. injection of Ko143 (Axon Medchem BV, The Netherlands) at a dose of 5 mg/kg
Summary
Inhibition of breast cancer resistance protein at the murine blood-brain barrier by Ko143 studied with [11C]tariquidar and PET. Joint meeting with the Hungarian Society of Experimental and Clinical Pharmacology (MFT) Innsbruck, Austria. 29-30 September 2011
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