The multidrug-resistant phenotype is characterized by the reduced intracellular retention of several structurally and functionally unrelated cytotoxic compounds due to the energy-dependent pump activity of P- glycoprotein (Pgp). Because (99m)Tc-sestamibi is a suitable transport substrate of Pgp, we tested whether the time-dependent fractional retention of this tracer could be used as an index of Pgp expression in untreated breast carcinomas. Methods: Twenty-seven patients with histologically confirmed breast carcinoma were intravenously injected with 740 MBq (20 mCi) of (99m)Tc-sestamibi, and static planar images of the breast were obtained at 10, 60 and 240 min. The fractional retention of (99m)Tc-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 counts/pixel registered in the region of interest drawn around the tumor. Surgically excised tumors were then obtained from each patient, and Pgp levels were determined using 125I- labeled MRK16 monoclonal antibody and in vitro quantitative autoradiography. Results: The fractional retention of (99m)Tc-sestamibi at 60 and 240 min was significantly higher in tumors with low Pgp levels (Group I, n = 18) as compared to that measured in tumors with high Pgp expression (Group II, n = 9) (13 <0,001). In particular, R60/10 values were 0.86 and 0.59 in breast carcinomas of Groups I and II, respectively, whereas the values of R240/10 were 0.55 and 0.25 in low- and high-Pgp-expressing tumors, respectively. Conclusion: The determination of fractional retention of (99m)Tc-sestamibi may be used as a simple functional test for Pgp expression in untreated breast cancer. A preliminary estimate of the sensitivity and the specificity of the test indicates its potential use in clinical practice to identify patients with a high probability of developing multidrug resistance.
|Number of pages||4|
|Journal||Journal of Nuclear Medicine|
|Publication status||Published - Sep 1997|
- Breast carcinoma
- Multidrug resistance
ASJC Scopus subject areas
- Radiological and Ultrasound Technology