Acquired Multi-Drug Resistance

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Anthracycline based therapy is a mainstay for many patients with solid tumor cancers. However, many of these tumors have variable levels of multiple drug resistance (MDR) transporters that reduce treatment effectiveness. The P-glycoprotein (Pgp) system specifically acts as a membrane pump to exclude anthracyclines and other common chemo therapeutics from intracellular accumulation. The activity of this transporter system can be up-regulated after exposure to anthracycline treatment and this is a suspected variable in treatment resistance and failure. In this project, we will quantify Pgp activity using a known transporter substrate, [[11]C]-verapamil, for tumor imaging. The uptake kinetics of this imaging agent can be used to quantify tissue Pgp activity when the tumor area under the curve from 0 to 20 min (AUC{0-20}) is normalized to the same AUC for blood. Imaging in sarcoma patients showed a range of [