TC-99M SESTAMIBI UPTAKE IN HUMAN BREAST-CARCINOMA CELL-LINES DISPLAYING GLUTATHIONE-ASSOCIATED DRUG-RESISTANCE

An in vitro study was designed to evaluate the uptake of sestamibi (MI BI) 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 adr iamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan- resistant (MCF7/mph) cells with increased levels of GSH. The effects o f buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells we re incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetiu m-99m MIBI. Both MIBI and Tl-201 uptakes were higher for MCF7/mph cell s than for the other cells studied. The mean MIBI uptake in MCF7/adr c ells was significantly lower than that in MCF7/wt cells (1.9%+/-0.5% v s 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 cell s with BSO resulted in a significant reduction in GSH content (from 24 3.2+/-81.1 nmol/mg protein to 17.6+/-4.4 nmol/mg protein; P <0.001). H owever, MIBI uptake in BSO-treated and untreated MCF7/mph cells was si milar (4.43%+/-0.5% and 5.93%+/-1.7%, respectively; P >0.1). This stud y suggests that the uptake of MIBI is not diminished by glutathione-as sociated drug resistance and that MIBI uptake in a tumour sample does not necessarily indicate that a cancer is sensitive to drugs.