Functional Imaging of Multidrug Resistance in Breast Cancer with PET
Abstract
The objective of this project is the development of a PET radiopharmaceutical for measuring 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. Single-photon myocardial perfusion agents such as 99mmTc-MIBI are substrates for Pgp, the protein implicated in mdr, and are now being studied for evaluation of mdr. A PET mdr tracer would provide significant advantages over 99mmTc-MIBI, and the half-life of 64Cu (12.7 h) is better matched to the apparent biological half-life of the mdr process in breast cancer (-240 min.) than are other PET radionuclides (e.g., 64C, T1/2= 11 min). We are carrying out in vivo and in vitro studies of lipophilic cat ionic 64Cu-based PET radiopharmaceuticals as potential PET mdr radiopharmaceuticals using murine (MAT-13) and human (MCF-7) breast cancer models. In vitro studies of prototype 64Cu complexes reveal a pattern of uptake similar to that observed for 99mmTc-MIBI. Studies are currently underway to determine the optimal chemical properties of this agent. The development of a radiopharmaceutical for the measurement of the mdr status of breast cancer lesions will facilitate optimization of treatment protocols, monitoring of the development of acquired resistance, and real-time evaluation of mdr modulators.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA404609
Entities
People
- Alan B. Packard