J R Ballinger1, T Muzzammil, M J Moore. 1. Faculty of Pharmacy, University of Toronto, Department of Oncologic Imaging, Princess Margret Hospital, Ontario, Canada.
Abstract
UNLABELLED: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Furifosmin is suitable for functional imaging of multidrug resistance in tumors.
UNLABELLED: 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. METHODS: 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. RESULTS: 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). CONCLUSION:Furifosmin is suitable for functional imaging of multidrug resistance in tumors.
Authors: Douglas S MacPherson; Kimberly Fung; Brendon E Cook; Lynn C Francesconi; Brian M Zeglis Journal: Dalton Trans Date: 2019-10-07 Impact factor: 4.390
Authors: Zhonglin Liu; Gail D Stevenson; Harrison H Barrett; Lars R Furenlid; Donald W Wilson; George A Kastis; Michael Bettan; James M Woolfenden Journal: Nucl Med Biol Date: 2005-08 Impact factor: 2.408
Authors: Zhonglin Liu; Gail D Stevenson; Harrison H Barrett; George A Kastis; Michael Bettan; Lars R Furenlid; Donald W Wilson; James M Woolfenden Journal: Nucl Med Biol Date: 2004-01 Impact factor: 2.408