Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications.
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.
Kannan
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P
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
John
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C
Zoghbi
S S
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Halldin
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Gottesman
M M
MM
Innis
R B
RB
Hall
M D
MD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism; D018432:Drug Resistance, Multiple; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D010599:Pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019275:Radiopharmaceuticals