Technetium-99m-furifosmin as an agent for functional imaging of multidrug resistance in tumors.
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).


CONCLUSIONS
Furifosmin is suitable for functional imaging of multidrug resistance in tumors.
Ballinger
J R
JR
Faculty of Pharmacy, University of Toronto, Department of Oncologic Imaging, Princess Margret Hospital, Ontario, Canada.
Muzzammil
T
T
Moore
M J
MJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005663:Furans; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy; D009368:Neoplasm Transplantation; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D011916:Rats, Inbred F344; D017256:Technetium Tc 99m Sestamibi; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D005663:Furans; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C078496:technetium Tc 99m Q12; C078700:technetium tc-99m tetrofosmin; D017256:Technetium Tc 99m Sestamibi; C070272:valspodar