P-glycoprotein (P-gp) is a major efflux transporter at the blood-brain barrier (BBB) where it controls the brain distribution of many drugs. Clinical translation of preclinical data obtained using invasive methods in animals is difficult due to species differences in P-gp expression and function. Positron emission tomography (PET) is an imaging technique allowing for the determination of the tissue kinetics of microdose of radiolabeled compounds. Three radiolabeled substrates of the P-gp have been developed for clinical use: [11C]verapamil, [11C]-N-desmethyl-loperamide and [11C]metoclopramide. These innovative tools enabled the study of P-gp in humans in various patho-physiological conditions including neurological diseases. This approach is also useful to predict the risk for drug-drug interaction caused by P-gp inhibitors at the BBB and address its impact for neuropharmacokinetics in vivo in humans.
Keywords: Barrière hémato-encéphalique; Blood-brain barrier; Imagerie; Imaging; P-glycoprotein; P-glycoprotéine; Pharmaco-imagerie; Pharmacocinétique; Pharmacokinetics; Pharmacological imaging; Radiopharmaceutique; Radiotracer; Transporter; Transporteur.
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