Molecular imaging of integrins in oncology

Carsten Höltke,¹ Andreas Faust<sup>2

1</sup>Department of Clinical Radiology, University Hospital Münster, and ²European Institute for Molecular Imaging, University of Münster, Münster, Germany

Abstract: Integrins are a class of heterodimeric cell surface receptors with a variety of essential contributions to cell–cell and cell–extracellular matrix interactions. In particular, integrin α_vβ₃ plays an important role in the regulation of normal and tumor cell migration and survival, as well as in tumor angiogenesis and metastasis. Its overexpression has been proved for a number of malignancies, and the level of α_vβ₃ expression has been recognized as a potential surrogate marker of angiogenic activity. Therefore, α_vβ₃ represents an important target structure in noninvasive cancer diagnosis and the evaluation of antiangiogenic therapies. One common feature of many integrins is high-affinity binding to proteins containing an Arg-Gly-Asp (RGD) peptide motif, which can be found in their endogenous ligands, for example, fibronectin, vitronectin, and fibrinogen. Consequently, not only small synthetic peptides containing the RGD motif but also peptidomimetic structures based on RGD have been designed, and appropriate labeling strategies utilized them for molecular imaging approaches. This review focuses on recent advances of integrin molecular imaging in cancer diagnosis. First, clinical applications are highlighted, and then experimental approaches in preclinical research and multimodal setups are discussed.

Keywords: integrins, angiogenesis, RGD, cancer diagnostics