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

Monica Piras, Andrea Testa, Ian N Fleming, Sergio Dall'Angelo, Alexandra Andriu, Sergio Menta, Mattia Mori, Gavin D. Brown, Duncan Forster, Kaye J. Williams, Matteo Zanda

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11 Citations (Scopus)
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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
Pages (from-to)1142-1151
Number of pages10
Issue number14
Early online date3 Jul 2017
Publication statusPublished - 20 Jul 2017

Bibliographical note

We thank The Development Trust, University of Aberdeen, for financial support and a fellowship to M.P. The work was also supported by the CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester (KJW Co-I; reference 16465). We thank Dr Massimiliano Baldassarre (University of Aberdeen) for helpful discussions.


  • imaging
  • positron emission tomography
  • integrin
  • tumour metastasis
  • angiogenesis


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