Development of Cu-64 Labeled EGF for In Vivo PET Imaging of EGFR Expression
The DOE is seeking radiolabeled compounds that have applications as radiotracers for radionuclide imaging technologies, such as positron emission tomography and single photon emission computed tomography. In response, this project will develop 64Cu-labeled epidermal growth factor (EGF) as a targeted PET radiotracer for imaging EGF receptors in cancer patients. The EGF receptor (EGFR) plays a crucial role in many cancers and is the major target for existing and emerging drugs. However, these drugs work in only 10-25% of patients. To reduce the treatment burden for non-responsive patients, and to decrease overall healthcare expenses, the proposed, targeted 64Cu PET radiotracer will be used to identify responsive patients and to monitoring the results of treatment with EGFR-directed drugs. The tracer will be based on a natural EGFR ligand that is site-specifically modified with a radionuclide chelator via a polyethyleneglycol linker. The approach will: (1) retain high-affinity EGFR binding of its natural ligand; (2) decrease non-specific tracer accumulation, thereby minimizing radiation exposure for non-targeted organs; and (3) eliminate radiosynthesis, thereby reducing the preparation of the EGFR-targeted PET radiotracer to a routine procedure that can be performed immediately before imaging. Phase I will validate the EGF-based 64Cu PET radiotracer in vitro and in mouse tumor models. In Phase II, the tracer will be developed for clinical trials. Commercial Applications and other Benefits as described by the awardee: Based on the current cost of PET contrast agents (~$500/scan) and an estimated 2,000,000 PET scans by 2010, the supply of a PET reagent for molecular imaging of the major drug targets should be a commercial success.
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