High Affinity “Click” RGD Peptidomimetics as Radiolabeled Probes for Imaging αvβ3 Integrina

Monica Piras, Andrea Testa, IN Fleming, Sergio Dall'Angelo, Alexandra Andriu, Sergio Menta, M. Mori, Gavin Brown, Duncan Forster, Kaye Williams, Matteo Zanda

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Non-peptidic RGD-mimic ligands were designed and synthesized by click chemistry between an arginine-azide mimic and an aspartic acid-alkyne mimic. Some of these molecules combine excellent in vitro properties (high αvβ3 affinity, selectivity, drug-like logD, high metabolic stability) with a variety of radiolabeling options (e.g. tritium and [18F]fluorine, plus compatibility with radio-iodination), not requiring the use of chelators or prosthetic groups. The binding mode of the resulting triazole RGD-mimics to αvβ3 or αIIbβ3 receptors was investigated by molecular modeling simulations. Compound 12 was successfully radiofluorinated and used for in vivo PET/CT studies in U87-tumour models, which showed only modest tumour uptake and retention, owing to rapid excretion. These results demonstrate that the novel click-RGD mimics are excellent radiolabeled probes for in vitro and cell-based studies on αvβ3 integrin, whereas further optimization of their pharmaco-kinetic and dynamic profile would be necessary for a successful use in in vivo imaging.
Original languageEnglish
Early online date3 Jul 2017
Publication statusPublished - 2017


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