Integrins avb3, avb5 and a5b1, key mediators of cell adhesion, differentiation, proliferation, angiogenesis and tumor growth, have been considered very promising targets for theranostic application. Due to the similarity of the RGD binding regions in these integrins, the development of synthetic molecules with high activity and selectivity for the different subtypes is a tricky goal to pursue. The majority of the ligands described so far as selective integrin targeting has in fact residual, yet significant, affinity for the other integrins, thus stimulating extensive research to develop novel integrin specific molecules.

In 2006 our research group designed by rational approach, in collaboration with IC-CNR, and synthesized the first avb3 selective peptide, referred as RGDechi, a chimeric molecule encompassing a cyclic portion containing the RGD triade for integrin binding and a linear sequence derived from the C-terminal fragment of the echistatin protein to confer specificity for b3 subunit. RGDechi was opportunely labelled and deeply characterized both in preclinical in vitro and in vivo cancer models. In order to improve its enzymatic stability and pharmacokinetic properties, chemical modifications were also introduced.