A new and selective radiolabeled αVβ3 peptide antagonist as tracer in tumor diagnosis

Abstract

Introduction Angiogenesis, the process whereby new capillaries are formed by outgrowth from existing microvessels, is required for tumor growth and metastasis [1,2]. The transmembrane cell-surface receptor αvβ3 has recently received increasingly attention, because of the critical role in tumor associated angiogenesis and metastasis formation. The restricted expression of integrin αVβ3 during tumor growth, invasion, and metastasis presents an interesting target for both detection and treatment of solid tumors [3]. Targeting αVβ3 with radiolabelled ligands may provide information about the receptor status and enable the planning and the monitoring of therapeutic approaches. Recently we developed a novel αVβ3 antagonist that showed a high selectivity for the receptor [4]. Adhesion assays, competitive binding assays and cross-linking experiments performed in human erythroleukemia K562 cells, stably cotransfected with cDNA of αv or αIIb and β3, demonstrated the high selectivity for αvβ3 integrin [4]. Starting from these evidences RGDechi was covalently bound to the chelating agent DTPA (Diethylene Triamine Pentaacetic Acid ) able to give stable complexes of radionuclides such as In and Y. The final goal has been to obtain a radiolabelled compound to be used in nuclear medicine as diagnostic and therapeutic agent. In particular DTPA-RGDechi has been labelled with In and used in SPECT (Single Photon Emission Computed Tomography) for diagnostic purpose. Moreover, the ligand RGDechi has been labelled with F for micro-PET in order to evaluate the use of this peptide for in vivo imaging.