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Advances in PET Imaging of P-Glycoprotein Function at the Blood-Brain Barrier

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† Department of Public Health and Caring Sciences, Uppsala University, Rudbecklaboratoriet, 751 85 Uppsala, Sweden
‡ PET Centre, Uppsala University Hospital, 751 85 Uppsala, Sweden
§ Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjöldsv 14C, 751 83 Uppsala, Sweden
*Fax: +46 18 471 4808. Telephone: +46 18 471 5038. E-mail: [email protected]
Cite this: ACS Chem. Neurosci. 2013, 4, 2, 225–237
Publication Date (Web):November 25, 2012
https://doi.org/10.1021/cn3001729
Copyright © 2012 American Chemical Society
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    Abstract

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    Efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) restricts substrate compounds from entering the brain and may thus contribute to pharmacoresistance observed in patient groups with refractory epilepsy and HIV. Altered P-gp function has also been implicated in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Positron emission tomography (PET), a molecular imaging modality, has become a promising method to study the role of P-gp at the BBB. The first PET study of P-gp function was conducted in 1998, and during the past 15 years two main categories of P-gp PET tracers have been investigated: tracers that are substrates of P-gp efflux and tracers that are inhibitors of P-gp function. PET, as a noninvasive imaging technique, allows translational research. Examples of this are preclinical investigations of P-gp function before and after administering P-gp modulating drugs, investigations in various animal and disease models, and clinical investigations regarding disease and aging. The objective of the present review is to give an overview of available PET radiotracers for studies of P-gp and to discuss how such studies can be designed. Further, the review summarizes results from PET studies of P-gp function in different central nervous system disorders.

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