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• W4255010805 endingPage "153535002002000" @default.
• W4255010805 startingPage "153535002002000" @default.
• W4255010805 abstract "Multidrug resistance (MDR) mediated by overexpression of MDR1 P-glycoprotein (Pgp) is one of the best characterized barriers to chemotherapy in cancer patients. Furthermore, the protective function of Pgp-mediated efflux of xenobiotics in various organs has a profound effect on the bioavailability of drugs in general. Thus, there is an expanding requirement to noninvasively interrogate Pgp transport activity in vivo. We herein report the Pgp recognition properties of a novel 99m Tc(I)-tricarbonyl complex, [ 99m Tc(CO) 3 (MIBI) 3 ] + (Tc-CO-MIBI). Tc-CO-MIBI showed 60-fold higher accumulation in drug-sensitive KB 3–1 cells compared to colchicine-selected drug-resistant KB 8-5 cells. In KB 8-5 cells, tracer enhancement was observed with the potent MDR modulator LY335979 (EC 50 = 62 nM). Similar behavior was observed using drug-sensitive MCF-7 breast adenocarcinoma cells and MCF-7/ MDR1 stable transfectants, confirming that Tc-CO-MIBI is specifically excluded by overexpression of MDR1 Pgp. By comparison, net accumulation in control H69 lung tumor cells was 9-fold higher than in MDR-associated protein ( MRP1)-expressing H69AR cells, indicating only modest transport by MRP1. Biodistribution analysis following tail vein injection of Tc-CO-MIBI showed delayed liver clearance as well as enhanced brain uptake and retention in mdr1a/1b(−/−) gene deleted mice versus wild-type mice, directly demonstrating that Tc-CO-MIBI is a functional probe of Pgp transport activity in vivo." @default.
• W4255010805 created "2022-05-12" @default.
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• W4255010805 date "2002-01-01" @default.
• W4255010805 modified "2023-09-27" @default.
• W4255010805 title "Characterization of a Novel^99mTc-Carbonyl Complex as a Functional Probe of<i>MDR1</i>P-Glycoprotein Transport Activity" @default.
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• W4255010805 doi "https://doi.org/10.1162/15353500200200002" @default.
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