Molecular imaging of epidermal growth factor receptor expression–activity at the kinase level in tumors with positron emission tomography

Because of the importance of epidermal growth factor receptor (EGFR) signaling pathway in oncogenesis, maintenance, and progression of different types of tumors, there has been an intense effort to develop non-invasive imaging approaches for selection and monitoring of EGFR-targeted therapies. During the past decade, EGFR-tyrosine kinase inhibitors have been explored as potential radiotracers for positron emission tomography (PET) imaging of EGFR over-expressing tumors. The development of agents for PET imaging of EGFR at the tyrosine kinase level has been so far based exclusively on anilinoquinazoline core structure, which has been “borrowed” as the key pharmacophore from the leading EGFR-inhibitory pharmaceuticals. The I-124, F-18, and C-11 radiolabeled irreversible inhibitors of EGFR demonstrate the greatest potential for derivatization into effective EGFR kinase imaging agents. PET imaging with radiolabeled agents specific for activated forms of EGFR kinase will facilitate the selection (stratification) of patients which will have more favorable responses to therapy with EGFR signaling inhibitors.