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• W1964505470 abstract "[18F]Fallypride ([18F]FP) is an important and routinely used D2/D3 antagonist for quantitative imaging of dopaminergic neurotransmission in vivo. Recently it was shown that the brain uptake of the structurally related [11C]raclopride is modulated by P-glycoprotein (P-gp), an important efflux transporter at the blood–brain barrier. The purpose of this study was to determine whether the brain uptake of [18F]FP is influenced by P-gp. For examination of this possible modulation microPET studies were performed in a rat and a mouse model. Hence, [18F]FP was applied to Sprague Dawley rats, half of them being treated with the P-gp inhibitor cyclosporine A (CsA). In a second experimental series the tracer was applied to three different groups of FVB/N mice: wild type, P-gp double knockout (abcb1a/1b (−/−)) and CsA-treated mice. In CsA-treated Sprague Dawley rats [18F]FP showed an elevated standard uptake value in the striatum compared to the control animals. In FVB/N mice a similar effect was observed, showing an increasing uptake from wild type to CsA-treated and double knockout mice. Since genetically or pharmacologically induced reduction of P-gp activity increased the uptake of [18F]FP markedly, we conclude that [18F]FP is indeed a substrate of P-gp and that the efflux pump modulates its brain uptake. This effect – if true for humans – may have particular impact on clinical studies using [18F]FP for assessment of D2/3 receptor occupancy by antipsychotic drugs. This article is part of the Special Issue Section entitled ‘Neuroimaging in Neuropharmacology’." @default.
• W1964505470 created "2016-06-24" @default.
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• W1964505470 date "2014-09-01" @default.
• W1964505470 modified "2023-10-18" @default.
• W1964505470 title "Evaluation of P-glycoprotein (abcb1a/b) modulation of [18F]fallypride in MicroPET imaging studies" @default.
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• W1964505470 doi "https://doi.org/10.1016/j.neuropharm.2013.04.062" @default.
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