FRACTIONAL RETENTION OF TECHNETIUM-99M-SESTAMIBI AS AN INDEX OF P-GLYCOPROTEIN EXPRESSION IN UNTREATED BREAST-CANCER PATIENTS

The multidrug-resistant phenotype is characterized by the reduced intr acellular retention of several structurally and functionally unrelated cytotoxic compounds due to the energy-dependent pump activity of P-gl ycoprotein (Pgp). Because Tc-99m-sestamibi is a suitable transport sub strate of Pgp, we tested whether the time-dependent fractional retenti on of this tracer could be used as an index of Pgp expression in untre ated breast carcinomas. Methods: Twenty-seven patients with histologic ally confirmed breast carcinoma were intravenously injected with 740 M Bq (20 mCi) of Tc-99m-sestamibi, and static planar images of the breas t were obtained at 10, 60 and 240 min. The fractional retention of Tc- 99m-sestamibi was then calculated as the ratios between 60 and 10 min (R60/10) and between 240 and 10 min (R240/10) of decay-corrected count s/pixel registered in the region of interest drawn around the tumor. S urgically excised tumors were then obtained from each patient, and Pgp levels were determined using I-125-labeled MRK16 monoclonal antibody and in vitro quantitative autoradiography. Results: The fractional ret ention of Tc-99m-sestamibi at 60 and 240 min was significantly higher in tumors with low Pgp levels (Group I, n = 18) as compared to that me asured in tumors with high Pgp expression (Group II, n = 9) (p < 0.001 ). In particular, R60/10 values were 0.86 and 0.59 in breast carcinoma s of Groups I and II, respectively, whereas the values of R240/10 were 0.56 and 0.25 in low-and high-Pgp-expressing tumors, respectively. Co nclusion: The determination of fractional retention of Tc-99m-sestamib i may be used as a simple functional test for Pgp expression in untrea ted breast cancer. A preliminary estimate of the sensitivity and the s pecificity of the test indicates its potential use in clinical practic e to identify patients with a high probability of developing multidrug resistance.