Ballinger J R, Bannerman J, Boxen I, Firby P, Hartman N G, Moore M J
Department of Nuclear Medicine, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Canada.
J Nucl Med. 1996 Sep;37(9):1578-82.
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.
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.
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.
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.
研究了99mTc-替曲膦（TFos）在大鼠MatB和人MCF-7乳腺癌细胞系的野生型（WT）和阿霉素耐药（AdrR）变体中的蓄积情况，以确定TFos是否像99mTc-司他莫比（MIBI）一样，是多药耐药转运蛋白P-糖蛋白（P-gp）的底物。
使用单细胞悬液（1×10⁶个细胞/ml），在37℃、有无P-gp强效调节剂PSC833的情况下，研究WT和AdrR细胞中TFos和MIBI在1小时内的蓄积时间进程。生成了PSC833、环孢素A和维拉帕米的调节剂剂量反应曲线。
在MatB和MCF-7细胞中，TFos和MIBI在WT细胞中大量蓄积，且蓄积不受PSC833影响。相比之下，AdrR细胞系对这两种示踪剂的蓄积都很少，但加入PSC833或其他调节剂后，这种蓄积呈剂量依赖性增加。TFos和MIBI的行为没有显著差异。
TFos与MIBI一样具有作为P-gp底物的特性，因此TFos可能有助于对肿瘤P-gp状态进行功能成像。
