Ballinger J R, Muzzammil T, Moore M J
Faculty of Pharmacy, University of Toronto, Department of Oncologic Imaging, Princess Margret Hospital, Ontario, Canada.
J Nucl Med. 1997 Dec;38(12):1915-9.
There has been a preliminary report that furifosmin, like the other lipophilic 99mTc cations sestamibi and tetrofosmin, is a substrate for P-glycoprotein, the membrane transporter that is a mechanism of multidrug resistance (MDR) in tumors. This has been further investigated in the rat mammary carcinoma cell line MatB/WT and its doxorubicin-selected resistant variant MatB/AdrR.
In vitro studies were performed by adding furifosmin to stirred single-cell suspensions of MatB/WT and MatB/AdrR in the presence or absence of the Pgp-modulating drug PSC833. Dynamic imaging studies over 30 min were performed in rats bearing MatB/WT or MatB/AdrR tumors growing in the leg.
Accumulation of furifosmin in MatB/AdrR cells in vitro was much lower than that in MatB/WT cells. The addition of 1 microM PSC833 increased the plateau accumulation in MatB/AdrR cells 2.4-fold, but did not affect accumulation in MatB/WT cells. In rats, furifosmin accumulated rapidly in MatB/WT tumors and washed out with a mean t3 of 78 min. Washout from MAtB/AdrR tumors was more rapid, with a t3 of 46 min (p < 0.025). Following dissection of animals at 30 min, mean tumor-to-muscle ratios were 1.57 and 1.05 in MatB/WT and MatB/ AdrR tumors, respectively (p < 0.025).
Furifosmin is suitable for functional imaging of multidrug resistance in tumors.
有初步报告称，呋磷胺与其他亲脂性99mTc阳离子司他米比和替曲膦一样，是P-糖蛋白的底物，P-糖蛋白是肿瘤多药耐药（MDR）的一种机制，即膜转运蛋白。这一点已在大鼠乳腺癌细胞系MatB/WT及其阿霉素选择的耐药变体MatB/AdrR中得到进一步研究。
在有或没有Pgp调节药物PSC833的情况下，将呋磷胺添加到MatB/WT和MatB/AdrR的搅拌单细胞悬浮液中进行体外研究。对腿部生长有MatB/WT或MatB/AdrR肿瘤的大鼠进行30分钟的动态成像研究。
体外MatB/AdrR细胞中呋磷胺的蓄积量远低于MatB/WT细胞。添加1μM PSC833可使MatB/AdrR细胞中的平台期蓄积量增加2.4倍，但不影响MatB/WT细胞中的蓄积量。在大鼠中，呋磷胺在MatB/WT肿瘤中迅速蓄积，平均t3为78分钟时洗脱。从MatB/AdrR肿瘤中洗脱更快，t3为46分钟（p<0.025）。在30分钟时解剖动物后，MatB/WT和MatB/AdrR肿瘤的平均肿瘤与肌肉比值分别为1.57和1.05（p<0.025）。
呋磷胺适用于肿瘤多药耐药的功能成像。
