, Volume 24, Issue 2, pp 150-159

In vivo detection of multidrug-resistant (MDR1) phenotype by technetium-99m sestamibi scan in untreated breast cancer patients

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Abstract

Technetium-99m sestamibi is a transport substrate recognised by the multidrug-resistant P-glycoprotein (Pgp). To test whether99mTc-sestamibi efflux is enhanced in breast carcinomas overexpressing Pgp, we determined the efflux rates of99mTc-sestamibi and Pgp levels in tumours from 30 patients with untreated breast carcinoma. Patients were intravenously injected with 740 MBq of99mTc-sestamibi and underwent a 15-min dynamic study followed by the acquisition of static planar images at 0.5, 1, 2 and 4 h. Tumour specimens were obtained from each patient 24 h after99mTc-sestamibi scan and Pgp levels were determined using125I-MRK16 monoclonal antibody and in vitro quantitative autoradiography. All breast carcinomas showed high uptake of99mTc-sestamibi and data from region of interest analysis on sequential images were fitted with a monoexponential function. The efflux rates of99mTc-sestamibi, calculated from decay-corrected time-activity curves, ranged between 0.00121 and 0.01690 min−1 and were directly correlated with Pgp levels measured in the same tumours (r=0.62;P<0.001). Ten out of 30 breast carcinomas (33%) contained 5 times more Pgp than benign breast lesions 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 concentration of 1.29±0.64 pmol/g (group B), equivalent to that found in benign breast lesions.99mTc-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 functional test with99mTc-sestamibi showed a sensitivity and a specificity of 80% and 95%, respectively. In conclusion, the efflux rate of99mTc-sestamibi may be used for the in vivo identification of the multidrug resistant (MDR1) phenotype in untreated breast cancer patients.