Abstract
An in vitro study was designed to evaluate the uptake of sestamibi (MIBI) 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 adriamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan-resistant (MCF7/mph) cells with increased levels of GSH. The effects of buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells were incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetium-99m MIBI. Both MIBI and201Tl uptakes were higher for MCF7/mph cells than for the other cells studied. The mean MIBI uptake in MCF7/adr cells was significantly lower than that in MCF7/wt cells (1.9%±0.5% vs 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 cells with BSO resulted in a significant reduction in GSH content (from 243.2±81.1 nmoUmg protein to 17.6±4.4 nmol/mg protein;P <0.001). However, MIBI uptake in BSO-treated and untreated MCF7/mph cells was similar (4.43%±0.5% and 5.93%±1.7%, respectively;P >0.1). This study suggests that the uptake of MIBI is not diminished by glutathione-associated drug resistance and that MIBI uptake in a tumour sample does not necessarily indicate that a cancer is sensitive to drugs.
References
Chan HSL, DeBoer G, Thorner PS, Haddad G, Gallie BL, Ling V. Multidrug resistance: clinical opportunities in diagnosis and circumvention.Hematol Oncol Clin North Am 1994; 8: 383–411.
Ford JM, Hait W. Pharmacology of drugs that alter multidrug resistance in cancer.Pharmacol Rev 1990; 42: 155–199.
Piwnica-Worms D, Kronauge JF, Chin ML. Uptake and retention of hexakis (2-methoxy isobutyl isonitrile) technetium (1) in cultured chick myocardial cells: mitochondrial and plasma membrane potential dependence.Circulation 1990; 82: 1826–1838.
Caner B, Kitapci M, Aras T, et al. Increased accumulation of hexakis (2-methoxy isobutyl isonitrile) technetium (1) in osteosarcoma and its metastatic lymph nodes.J Nucl Med 1991; 32:1977–1978.
Piwnica-Worms D, Chin ML, Budding J, et al. Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex.Cancer Res 1993; 53: 977–984.
Tow KD. Glutathione-associated enzymes in anticancer drug resistance.Cancer Res 1994; 54: 4313–4320.
Kramer RA, Zakher J, Kim G. Role of the glutathione redox cycle in acquired and de novo multidrug resistance.Science 1988;241:694–697.
Batist G, Schecter R, Woo A, Greene D, Lehnert S. Glutathione depletion in human and in rat multi-drug resistant breast cancer cell lines.Biochemical Pharmacol 1991; 41: 631–635.
Batist G, Tulpule A, Sinha BK, Katki AG, Myers CE, Cowan KH. Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells.J Biol Chem 1986; 261: 15554–15549.
Cordobes MD, Blanchot C, Celmon-Moingeon L, et al. Tc-99m MIBI uptake by a series of human benign and malignant breast tumor cells: correlation with gene MDR expression [abstract].Eur J Nucl Med 1994; 21: S8.
Dalton W. Drug resistance modulation in the laboratory and the clinic.Semin Oncol 1993; 20: 64–69.
Moretti JL, Çagçlar M, Boaziz C, Caillat-Vigneron N, Morere JF. Sequential functional imaging with technetium-99m hexakis-2-methoxyisobutylisonitrile and indium-111 octrootide: can we predict the response to chemotherapy in small cell lung cancer?Eur J Nucl Med 1995; 22: 177–180.
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Kabasakal, L., Özker, K., Hayward, M. et al. Technetium-99m sestamibi uptake in human breast carcinoma cell lines displaying glutathione-associated drug-resistance. Eur J Nucl Med 23, 568–570 (1996). https://doi.org/10.1007/BF00833393
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DOI: https://doi.org/10.1007/BF00833393