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Imaging the Function of P‐Glycoprotein With Radiotracers: Pharmacokinetics and In Vivo Applications
Author(s) -
Kannan P,
John C,
Zoghbi S S,
Halldin C,
Gottesman M M,
Innis R B,
Hall M D
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.138
Subject(s) - p glycoprotein , in vivo , positron emission tomography , efflux , pharmacokinetics , pharmacology , transporter , molecular imaging , preclinical imaging , atp binding cassette transporter , chemistry , emission computed tomography , medicine , cancer research , nuclear medicine , multiple drug resistance , biochemistry , biology , microbiology and biotechnology , gene , antibiotics
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. Clinical Pharmacology & Therapeutics (2009) 86 4, 368–377. doi: 10.1038/clpt.2009.138