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 [
Many tumors have variable levels of multiple drug resistance (MDR) transporters: that reduce treatment effectiveness for some chemotherapy protocols. The P-glycoprotein (Pgp) system specifically acts as a membrane pump to exclude drugs from intracellular accumulation. 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 as an important resistance factor. Imaging before treatment and after exposure to chemotherapy will measure the extent of acquired MDR and should be useful to modify chemotherapy
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