Imaging of human epidermal growth factor receptors for patient selection and response monitoring - From PET imaging and beyond

The Human Epidermal Growth Factor Receptor (ErbB/HER) family - EGFR/HER1, ErbB-2/HER2, ErbB-3/HER3, and ErbB-4/HER4 - play a key role in tumor development. Moreover, positive status of HER2 and specific mutations of EGFR are necessary to initiate HER2 directed and EGFR mutation directed therapies. The status of these receptors is usually determined by assaying biopsy specimens of tumor tissues; however, tissue samples are insufficient to account for the complex dynamics and heterogeneity involved in HER status. Molecular imaging of receptors of the HER family have undergone much development, and some show promise for facilitating patient selection for HER therapy and monitoring of treatment response. This review provides a general overview of HER family expression and signaling in tumor tissue and more importantly discusses the available EGFR, HER2 and HER3 molecular imaging modalities, highlighting their use not only for selecting patients for receptor-targeted therapy, but also for monitoring therapeutic response. Additionally, the design and the biological evaluation of HER-specific imaging probes using different cancer models and clinical data are discussed.