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The dependence of tumour growth and metastasis on blood vessels makes tumour angiogenesis a rational target for therapy. Imaging of αvβ3 expression could potentially be used as a biomarker and an early indicator of efficacy of antiangiogenic treatments at a molecular level. Research efforts have mainly focused on the development of RGD-based radiolabelled αvβ3 inhibitors suitable for PET and SPECT imaging modalities that, owing to their high sensitivity, represent the most powerful tool for monitoring in vivo tumour angiogenesis. The aim of this multidisciplinary project was the design, synthesis and biological evaluation of novel αvβ3 ligands as molecular imaging probes. Three classes of integrin antagonists were designed: 1) triazole-based RGD mimetics that can be isotopically-labelled with tritium, fluorine and iodine radioisotopes by means of highly practical procedures, 2) RGD peptidomimetics incorporating the metabolically stable 2,2,2-trifluoroethylamine function as a peptide bond bioisostere and 3) RGD cyclopeptides conjugated with FDR, a novel prosthetic group allowing glycosylation and 18F-fluorination of aminooxy-functionalised molecules in one synthetic step. RGD-based strategies have also been used for selective tumour delivery of chemotherapeutic agents. A number of cytotoxic drugs have been conjugated to RGD peptides, providing experimental evidence that αvβ3 targeted chemotherapy strategies could be used as a powerful tool to reduce the toxicity and augment the therapeutic window of existing cytotoxic agents. In this work, we described the rational design of a novel targeted cytotoxic conjugate containing a triazole-based RGD peptidomimetic as tumour-homing motif of the potent antimitotic agent, paclitaxel. Preliminary in vitro studies were performed to assess the therapeutic potential of this targeted cytotoxic construct.