title: Single photon emission computed tomography and positron emission tomography imaging of multi-drug resistant P-glycoprotein--monitoring a transport activity important in cancer, blood-brain barrier function and Alzheimer's disease.
abstract: Overexpression of multi-drug resistant P-glycoprotein (Pgp) remains an important barrier to successful chemotherapy in cancer patients and impacts the pharmacokinetics of many important drugs. Pgp is also expressed on the luminal surface of brain capillary endothelial cells wherein Pgp functionally comprises a major component of the blood-brain barrier by limiting central nervous system penetration of various therapeutic agents. In addition, Pgp in brain capillary endothelial cells removes amyloid-beta from the brain. Several single photon emission computed tomography and positron emission tomography radiopharmaceutical have been shown to be transported by Pgp, thereby enabling the noninvasive interrogation of Pgp-mediated transport activity in vivo. Therefore, molecular imaging of Pgp activity may enable noninvasive dynamic monitoring of multi-drug resistance in cancer, guide therapeutic choices in cancer chemotherapy, and identify transporter deficiencies of the blood-brain barrier in Alzheimer's disease.
authors.affiliation: Washington University Medical School, 510 South Kingshighway Boulevard, Box 8225, St. Louis, MO 63110, USA. piwnica-wormsd@mir.wustl.edu
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: Aparna H
authors.initials: AH
authors.lastname: Kesarwala
authors.forename: Andrea
authors.initials: A
authors.lastname: Pichler
authors.forename: Julie L
authors.initials: JL
authors.lastname: Prior
authors.forename: Vijay
authors.initials: V
authors.lastname: Sharma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D009553:Nimodipine / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009553:Nimodipine; D019275:Radiopharmaceuticals