Abstract
The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for repeatable whole-body assessment of the molecular disease profile, solving problems of heterogeneity and expression alterations over time. Tracer development is a multifactorial process. The optimal tracer design depends on the application and the particular challenges of the molecular target (target expression in tumors, endogenous expression in healthy tissue, accessibility). We have herein summarized the recent preclinical and clinical data on agents for Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) imaging of EGFR-family receptors in oncology. Antibody-based tracers are still extensively investigated. However, their dominance starts to be challenged by a number of tracers based on different classes of targeting proteins. Among these, engineered scaffold proteins (ESP) and single domain antibodies (sdAb) show highly encouraging results in clinical studies marking a noticeable trend towards the use of smaller sized agents for HER imaging.
Highlights
The four family members, HER1 ( ErbB1 or epidermal growth factor receptor (EGFR)), HER2 (ErbB2), HER3 (ErbB3), and HER4 (ErbB4) have a common structure consisting of an extracellular domain (ECD), a transmembrane domain, and an intracellular domain (ICD)
This review focuses on the recent progress in Positron Emission Tomography (PET) and SPECT imaging of EGFRfamily receptors HER1, HER2, HER3 using different types of targeting agents
The EGFR (RTK I) family takes a central role in oncogenic transformation
Summary
The human epidermal growth factor receptor (EGFR) family ( designated receptor tyrosine kinase (RTK) Class I, ErbB family or HER-family) is a class of tyrosine kinase receptors involved in fundamental cellular processes such as cell proliferation, migration, survival, and angiogenesis [1,2]. Domains I and III form a ligand binding pocket and expose subdomain II to enable dimerization with other family members [3,4,5,6,7,8]. Ligand binding and dimerization triggers biochemical downstream signaling by inducing kinase activity and phosphorylation of tyrosine residues on the intracellular c-terminal tail of the receptors [9,10]. HER3 lacks sufficient intracellular kinase activity and its signaling is, reliant on heterodimerization with other family members [11,12]. HER2 overexpression is most prominently associated with its role in breast cancer (BC), where it is over expressed in 15–20% of cases [23,25]. Small molecule tyrosine kinase inhibitors (TKI) can be used to suppress the intracellular kinase activity of EGFR-family receptors. Because the role of HER4 in cancer is still poorly understood, the development of targeting therapeutics is lacking
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