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Kinetic models for measuring P-glycoprotein function at the blood-brain barrier with Positron Emission Tomography
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. PET centre, Uppsala University Hospital.
2016 (English)In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 22, no 38, 5786-5792 p.Article in journal (Refereed) Published
Abstract [en]

P-glycoprotein function is associated with a number of neurodegenerative and psychiatric diseases as well as with pharmacoresistance to for example antiepileptic drugs. The ability to measure P-gp function in vivo would allow for an increased understanding of the mechanisms of disease and treatment. This review assesses the various approaches to in vivo quantification of P-gp function using currently available P-gp tracers and PET in humans. First, the use of compartment models, and their interpretation in terms of P-gp function at the blood-brain barrier, is discussed. Then, the methods that have been used to quantify PET data of the P-gp tracers [11C]verapamil, [11C]N-desmetyl-loperamide (dLop), [11C]laniquidar, [11C]phenytoin, [11C]tariquidar and [11C]elacridar are reviewed. In summary, the extraction of P-gp substrate PET tracers, which is their plasma to tissue rate constant K1 corrected for variations in regional cerebral blood flow, is generally considered to be the preferred measure of P-gp function.

Place, publisher, year, edition, pages
2016. Vol. 22, no 38, 5786-5792 p.
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-312407DOI: 10.2174/1381612822666160804093852ISI: 000389454900005PubMedID: 27494063OAI: oai:DiVA.org:uu-312407DiVA: diva2:1063228
Funder
EU, FP7, Seventh Framework Programme, 201380
Available from: 2017-01-09 Created: 2017-01-09 Last updated: 2017-02-09Bibliographically approved

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CiteExportLink to record
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Citation style
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