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Technetium-99m-tetrofosmin as a substrate for P-glycoprotein: in vitro studies in multidrug-resistant breast tumor
J R Ballinger1, J Bannerman, I Boxen
1Department of Nuclear Medicine, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Canada.
Unlabelled:
The accumulation of 99mTc-tetrofosmin (TFos) was studied in wildtype (WT) and doxorubicin-resistant (AdrR) variants of the rat MatB and human MCF-7 breast tumor cell lines to determine whether TFos, like 99mTc-sestamibi (MIBI), is a substrate for P-glycoprotein (P-gp), a multidrug-resistance transporter.
Methods:
The time course of accumulation of TFos and MIBI in WT and AdrR cells over 1 hr was studied using single-cell suspensions at 1 x 10(6) cells/ml incubated at 37 degrees C in the presence or absence of PSC833, a potent modulator of P-gp. Modulator dose-response curves were generated for PSC833, cyclosporin A, and verapamil.
Results:
In both MatB and MCF-7 cells, TFos and MIBI accumulated extensively in WT cells and accumulation was not affected by PSC833. In contrast, ADrR cell lines accumulated very little of either tracer, but addition of PSC833 or other modulator increased this accumulation in a dose-dependent fashion. TFos and MIBI did not differ significantly in their behavior.
Conclusion:
TFos shares with MIBI the property of being a substrate for P-gp and thus TFos may be useful for functional imaging of tumor P-gp status.