title: Imaging multidrug resistance P-glycoprotein transport function using microPET with technetium-94m-sestamibi.
abstract: The best characterized mechanism of multidrug resistance (MDR) in cancer involves the MDR1 efflux transporter P-glycoprotein (Pgp). The positron-emitting radiotracer hexakis(2-methoxyisobutylisonitrile)-(94m)Tc ((94m)Tc-MIBI) was synthesized and validated in cell transport studies as a substrate for MDR1 Pgp. In vivo small-scale PET imaging and biodistribution studies of mdr1a/1b (-/-) gene deleted and wild-type mice demonstrated the use of (94m)Tc-MIBI to detect Pgp function. The reversal effect of a Pgp modulator was shown in tissue distribution studies of KB 3-1 (Pgp-) and KB 8-5 (Pgp+) tumor-bearing nude mice. The current (94m)Tc-MIBI experiments parallel previous studies employing (99m)Tc-MIBI, showing essentially identical performance of the two technetium radiotracers and providing biological validation of (94m)Tc-MIBI for PET imaging of multidrug resistance.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, MO 63110, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Bigott
authors.forename: Julie L
authors.initials: JL
authors.lastname: Prior
authors.forename: David R
authors.initials: DR
authors.lastname: Piwnica-Worms
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D021381:Protein Transport; D011804:Quinolines / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000032:analysis* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013379:Substrate Specificity; D017256:Technetium Tc 99m Sestamibi / Q000032:analysis* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003986:Dibenzocycloheptenes; D011804:Quinolines; D019275:Radiopharmaceuticals; C095179:zosuquidar trihydrochloride; D017256:Technetium Tc 99m Sestamibi