title: Technetium-99m sestamibi uptake in human breast carcinoma cell lines displaying glutathione-associated drug-resistance.
abstract: An in vitro study was designed to evaluate the uptake of sestamibi (MIBI) in P-glycoprotein (Pgp) and glutathione-associated (GSH) multidrug-resistant (MDR) cell lines. MIBI uptake was studied in various human breast carcinoma cell lines, i.e. in wild-type (MCF7/wt) cells, in adriamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan-resistant (MCF7/mph) cells with increased levels of GSH. The effects of buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells were incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetium-99m MIBI. Both MIBI and 201Tl uptakes were higher for MCF7/mph cells than for the other cells studied. The mean MIBI uptake in MCF7/adr cells was significantly lower than that in MCF7/wt cells (1.9%+/-0.5% vs 3. 1%.0.6%; P <0.01). Verapamil treatment increased the MIBI uptake in MCF7/adr cells (to 2.6%.0.3%; P <0.05). Treatment of MCF7/mph cells with BSO resulted in a significant reduction in GSH content (from 243.2+/-81.1 nmol/mg protein to 17.6+/-4.4 nmol/mg protein; P <0. 001). However, MIBI uptake in BSO-treated and untreated MCF7/mph cells was similar (4.43%+/-0.5% and 5.93%+/-1.7%, respectively; P >0. 1). This study suggests that the uptake of MIBI is not diminished by glutathione-associated drug resistance and that MIBI uptake in a tumour sample does not necessarily indicate that a cancer is sensitive to drugs.
authors.affiliation: Department of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kabasakal
authors.forename: K
authors.initials: K
authors.lastname: Ozker
authors.forename: M
authors.initials: M
authors.lastname: Hayward
authors.forename: G
authors.initials: G
authors.lastname: Akansel
authors.forename: O
authors.initials: O
authors.lastname: Griffith
authors.forename: A T
authors.initials: AT
authors.lastname: Isitman
authors.forename: R
authors.initials: R
authors.lastname: Hellman
authors.forename: D
authors.initials: D
authors.lastname: Collier
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D011877:Radionuclide Imaging; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics; D013794:Thallium Radioisotopes / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013794:Thallium Radioisotopes; D017256:Technetium Tc 99m Sestamibi; D005978:Glutathione