TARGETING EPIDERMAL GROWTH FACTOR (EGF) RECEPTOR-POSITIVE TUMORS WITH ~64Cu AND ~86Y-LABELED MONOCLONAL ANTIBODY ERBITUX

摘要

Introduction: The epidermal growth factor receptor (EGFR) and its ligands have been recognized as critical factors in the pathophysiology of tumorigenesis and have been studied extensively. Over-expression of the EGFR plays a significant role in the tumor progression of a wide variety of solid human cancers. Therefore, the EGFR represents an attractive target for the design of novel anticancer diagnostic and therapeutic agents, including monoclonal antibodies and small molecule inhibitors. The capacity of anti-EFGR agents, such as Erbitux (Cetuximab), have been well established to slow tumor cell proliferation and modulate cell cycle phase distribution as well as cause significant growth inhibition in tumor cell lines and xenografts. The effective use of Erbitux will depend on the ability of physicians to detect and characterize EGFR-expressing lesions before and after the initiation of EGFR-directed treatments. Our goal is to image the over-expression of EGFR in tumors by Positron Emission Tomography (PET) with ~64Cu- and ~85Y-labeled Erbitux. PET imaging based on the binding, internalization, and retention of the radiolabeled, anti-EGFR antibody in intracellular compartments will provide a much-needed, quantitative, non-invasive in vivo method of evaluating EGFR. This allows for a better prediction of both efficacy and toxicity of the anti-EGFR antibody treatment.