Abstract
Abstract : The object 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 99mTc-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 99mTc- 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 (-24O min.) than are other PET radionuclides (e.g., 11C, T1/2= 11 min). We are carrying out in vivo and in vitro studies of lipophilic cationic 64Cu-based PET radiopharmaceuticals as potential PET mdr radiopharmaceuticals using murine (MAT-B) and human (MCF-7) breast cancer models. In vitro studies of prototype 64Cu-based complexes reveal a pattern of uptake similar to that observed for 99mTc-MIBI. Studies are currently underway to determine that optimal chemical properties of this agent. The development of a radiopharmaceuticals 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.
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