title: Characterization of P-glycoprotein transport and inhibition in vivo.
abstract: The P-glycoprotein is an energy-dependent efflux pump capable of decreasing the intracellular concentration of a broad range of chemotherapeutic agents. [99mTc]Sestamibi, a P-glycoprotein transport substrate, is a sensitive probe of P-glycoprotein function both in vitro and in vivo. A human tumor model in nude mice was evaluated to determine whether [99mTc]Sestamibi could detect in vivo differences in P-glycoprotein expression and P-glycoprotein modulation by the reversal agent SDZ PSC 833. Differential [99mTc]Sestamibi accumulation based upon P-glycoprotein expression was demonstrated in xenografts in vivo. Dose-dependent inhibition of P-glycoprotein function was achieved with SDZ PSC 833. Administration of the reversal agent increased [99mTc]Sestamibi accumulation in the xenografts expressing P-glycoprotein. These observations show that [99mTc]Sestamibi as capable of detecting the modulation of P-glycoprotein in a solid tumor model by the reversal agent SDZ PSC 833.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: E
authors.initials: E
authors.lastname: Barbarics
authors.forename: J F
authors.initials: JF
authors.lastname: Kronauge
authors.forename: D
authors.initials: D
authors.lastname: Cohen
authors.forename: A
authors.initials: A
authors.lastname: Davison
authors.forename: A G
authors.initials: AG
authors.lastname: Jones
authors.forename: J M
authors.initials: JM
authors.lastname: Croop
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000378:metabolism; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; C070272:valspodar