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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.

Inhibition of breast cancer resistance protein at the murine blood-brain barrier by Ko143 studied with [11C]tariquidar and PET