CHARACTERIZATION OF P-GLYCOPROTEIN TRANSPORT AND INHIBITION IN-VIVO

The P-glycoprotein is an energy-dependent efflux pump capable of decre asing the intracellular concentration of a broad range of chemotherape utic agents, [Tc-99m]Sestamibi, a P-glycoprotein transport substrate, is a sensitive probe of P-glycoprotein function both in vitro and in v ivo. A human tumor model in nude mice was evaluated to determine wheth er [Tc-99m]Sestamibi could detect in vivo differences in P-glycoprotei n expression and P-glycoprotein modulation by the reversal agent SDZ P SC 833, Differential [Tc-99m]Sestamibi accumulation based upon P-glyco protein expression was demonstrated in xenografts in vivo, Dose-depend ent inhibition of P-glycoprotein function was achieved with SDZ PSC 83 3, Administration of the reversal agent increased [Tc-99m]Sestamibi ac cumulation in the xenografts expressing P-glycoprotein. These observat ions show that [Tc-99m]Sestamibi as capable of detecting the modulatio n of P-glycoprotein in a solid tumor model by the reversal agent SDZ P SC 833.