Functional Imaging of Multidrug Resistance in Breast Cancer wit PET
Abstract
The objective of this project is the development of a PET radiopharmaceutical for the evaluation of multidrug resistance (mdr) in breast cancer. Multidrug resistance is resistance of a lesion to a specific class of drugs that includes many of the chemotherapeutics that are most effective against breast cancer and is characterized by the increased concentration of P-glycoprotein (Pgp), a 170 kD transmembrane glycoprotein, which reduces the intracellular concentration of these drugs to non-toxic levels. Lipophilic cationic complexes such as Tc-99m-MIBI are substrates for Pgp and are now being studied for evaluation of mdr function in vivo. We are currently carrying out in vivo and in vitro studies of lipophilic cationic Cu-64-based PET mdr radiopharmaceuticals as possible PET mdr radiopharmaceuticals. A PET mdr tracer will provide significant advantages over Tc-9mm-MIBI, and the half-life of Cu-64 (12.7 h) is better matched to the apparent biological half-life of the mdr process (approx. 240 min.) than are other PET radionuclides (e.g., C-11, T 1/2 = 11 min). These radiopharmaceuticals may provide information about the mdr status of breast cancer lesions that will allow optimization of treatment protocols, monitoring of the development of acquired resistance, and real-time evaluation of the effectiveness of drugs developed to modulate mdr.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA385729
Entities
People
- Alan Packard