IN-VIVO DETECTION OF MULTIDRUG-RESISTANT (MDR1) PHENOTYPE BY TC-99M SESTAMIBI SCAN IN UNTREATED BREAST-CANCER PATIENTS

Technetium-99m sestamibi is a transport substrate recognised by the mu ltidrug-resistant P-glycoprotein (Pgp). To test whether Tc-99m-sestami bi efflux is enhanced in breast carcinomas overexpressing Pgp, we dete rmined the efflux rates of Tc-99m-sestamibi and Pgp levels in tumours from 30 patients with untreated breast carcinoma. Patients were intrav enously injected with 740 MBq of Tc-99m-sestamibi and underwent a 15-m in dynamic study followed by the acquisition of static planar images a t 0.5, 1, 2 and 4 h. Tumour specimens were obtained from each patient 24 h after Tc-99m-sestamibi scan and Pgp levels were determined using I-125-MRK16 monoclonal antibody and in vitro quantitative autoradiogra phy. All breast carcinomas showed high uptake of Tc-99m-sestamibi and data from region of interest analysis on sequential images were fitted with a monoexponential function. The efflux rates of Tc-99m-sestamibi , calculated from decay-corrected time-activity curves, ranged be twee n 0.00121 and 0.01690 min(-1) and were directly correlated with Pgp le vels measured in the same tumours (r=0.62; P<0.001). Ten out of 30 bre ast carcinomas (33%) contained 5 times more Pgp than benign breast les ions and showed a mean concentration of 5.73+/-1.63 pmol/g of tumour ( group A). The remaining 20 breast carcinomas had a mean Pgp concentrat ion of 1.29+/-0.64 pmol/g (group B), equivalent to that found in benig n breast lesions. Tc-99m-sestamibi efflux from tumours of group A was 2.7 times higher than that observed in tumours of group B (0.00686+/-0 .00390 min(-1) vs 0.00250+/-0.00090 min(-1), P<0.001). The in vivo fun ctional test with Tc-99m-sestamibi showed a sensitivity and a specific ity of 80% and 95%, respectively. In conclusion, the efflux rate of Tc -99m-sestamibi may be used for the in vivo identification of the multi drug resistant (MDR1) phenotype in untreated breast cancer patients.