Technetium-99m-tetrofosmin as a substrate for P-glycoprotein: In vitro studies in multidrug resistant breast tumor cells

被引:0
作者
Ballinger, JR
Bannerman, J
Boxen, I
Firby, P
Hartman, NG
Moore, MJ
机构
[1] PRINCESS MARGARET HOSP,ONTARIO CANC INST,DEPT NUCL MED,TORONTO,ON M4X 1K9,CANADA
[2] PRINCESS MARGARET HOSP,ONTARIO CANC INST,DEPT EXPT THERAPEUT,TORONTO,ON M4X 1K9,CANADA
[3] PRINCESS MARGARET HOSP,ONTARIO CANC INST,DEPT MED,TORONTO,ON M4X 1K9,CANADA
[4] UNIV TORONTO,FAC PHARM,TORONTO,ON M5S 1A1,CANADA
[5] UNIV TORONTO,FAC MED,TORONTO,ON M5S 1A1,CANADA
[6] NOTRE DAME HOSP,DEPT NUCL MED,MONTREAL,PQ,CANADA
关键词
technetium-99m-tetrofosmin; technetium-99m-sestamibi; multidrug resistance;
D O I
暂无
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
The accumulation of Tc-99m-tetrofosmin (TFos) was studied in wild-type (WT) and doxorubicin-resistant (Adr(R)) variants of the rat MatB and human MCF-7 breast tumor cell lines to determine whether TFos, like Tc-99m-sestamibi (MIBI), is a substrate for P-glycoprotein (P-gp), a multidrug-resistance transporter. Methods: The time course of accumulation oi TFos and MIBI in WT and Adr(R) 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, Adr(R) 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.
引用
收藏
页码:1578 / 1582
页数:5
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