Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8536772 | Pharmacology & Therapeutics | 2018 | 69 Pages |
Abstract
Transporter systems involved in the permeation of drugs and solutes across biological membranes are recognized as key determinants of pharmacokinetics. Typically, the action of membrane transporters on drug exposure to tissues in living organisms is inferred from invasive procedures, which cannot be applied in humans. In recent years, imaging methods have greatly progressed in terms of instruments, synthesis of novel imaging probes as well as tools for data analysis. Imaging allows pharmacokinetic parameters in different tissues and organs to be obtained in a non-invasive or minimally invasive way. The aim of this overview is to summarize the current status in the field of molecular imaging of drug transporters. The overview is focused on human studies, both for the characterization of transport systems for imaging agents as well as for the determination of drug pharmacokinetics, and makes reference to animal studies where necessary. We conclude that despite certain methodological limitations, imaging has a great potential to study transporters at work in humans and that imaging will become an important tool, not only in drug development but also in medicine. Imaging allows the mechanistic aspects of transport proteins to be studied, as well as elucidating the influence of genetic background, pathophysiological states and drug-drug interactions on the function of transporters involved in the disposition of drugs.
Keywords
ABCOCTNMAG3OATPP-gpTKIBcrpMRPBPNDDDIPBPKSLCADMECyPMDRAUCmercaptoacetyltriglycineP-glycoproteinAdenosine TriphosphateATPMRIOctSPECTAlzheimer's diseaseMagnetic resonance imagingMolecular imagingdrug-drug interactionsingle photon emission computed tomographycomputed tomographyPositron emission tomographyabsorption, distribution, metabolism and eliminationOatsolute carrierorganic cation transporterorganic anion transporterMembrane transportersMateBBBCytochrome P450PharmacokineticsPhysiologically based pharmacokineticBlood-brain barrierMultidrug resistancearea under the curveTyrosine kinase inhibitorPETnon-displaceable binding potentialmultidrug resistance-associated proteinbreast cancer resistance proteinorganic anion-transporting polypeptideSingle nucleotide polymorphismSNPorganic cation/carnitine transportertotal clearanceATP-binding cassette
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Authors
Nicolas Tournier, Bruno Stieger, Oliver Langer,