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Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications. | LitMetric

Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications.

Clin Pharmacol Ther

Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.

Published: October 2009

AI Article Synopsis

Article Abstract

P-glycoprotein (P-gp), an efflux transporter, controls the pharmacokinetics of various compounds under physiological conditions. P-gp-mediated drug efflux has been suggested as playing a role in various disorders, including multidrug-resistant cancer and medication-refractory epilepsy. However, P-gp inhibition has had, to date, little or no clinically significant effect in multidrug-resistant cancer. To enhance our understanding of its in vivo function under pathophysiological conditions, substrates of P-gp have been radiolabeled and imaged using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). To accurately quantify P-gp function, a radiolabeled P-gp substrate should be selective for P-gp, produce a large signal after P-gp blockade, and generate few radiometabolites that enter the target tissue. Furthermore, quantification of P-gp function via imaging requires pharmacological inhibition of P-gp, which requires knowledge of P-gp density at the target site. By meeting these criteria, imaging can elucidate the function of P-gp in various disorders and improve the efficacy of treatments.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746858PMC
http://dx.doi.org/10.1038/clpt.2009.138DOI Listing

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