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Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications Kannan P; John C; Zoghbi SS; Halldin C; Gottesman MM; Innis RB; Hall MDClin Pharmacol Ther 2009[Oct]; 86 (4): 368-77P-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.|*Radiopharmaceuticals/pharmacokinetics[MESH]|ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism[MESH]|Alzheimer Disease/drug therapy/metabolism[MESH]|Biological Transport/physiology[MESH]|Blood-Brain Barrier/metabolism[MESH]|Drug Resistance, Multiple[MESH]|Epilepsy/drug therapy/metabolism[MESH]|Humans[MESH]|Models, Biological[MESH]|Neoplasms/drug therapy/metabolism[MESH]|Parkinson Disease/drug therapy/metabolism[MESH]|Pharmacokinetics[MESH]|Positron-Emission Tomography[MESH]|Tomography, Emission-Computed, Single-Photon[MESH] |
