Synthesis and Characterization of a Selective Alpha(v)Beta(3) Receptor Cyclic Peptide Antagonist Functionalized with a Chelating Group for Metal Labelling

  • Luca Monfregola
  • Michele Saviano
  • Stefania De Luca


Small radiolabelled compounds such as peptides are very attractive tools for the diagnosis of several different pathologies (Heppeler in Curr Med Chem 7:971–994, 2000). Among the possible biological targets for radiolabelled compounds, the alpha(v)beta(3) (αvβ3) integrin cell adhesion receptor has been extensively studied. It is expressed on proliferating but not quiescent endothelial cells and has been shown to be involved in tumour progression, angiogenesis and metastasis. The novel radioactive probe 111In-DTPA-RGDechi has been successfully employed for selective αvβ3 single-photon imaging studies. Herein we report the efficient synthetic protocol developed in order to obtain the conjugate diethylentriaminopentacetic acid (DTPA)-RGDechi in good yield and high purity.


Solid phase synthesis Selective radioactive probe αvβ3 Receptor 


  1. Albelda SM, Mette SA, Elder DE et al (1990) Integrin distribution in malignant melanoma: association of the β3 subunit with tumor progression. Cancer Res 50:6757–6764PubMedGoogle Scholar
  2. Benneth JS (2005) Structure and function of the platelet integrin αIIbβ3. J Clin Invest 115:3363–3369CrossRefGoogle Scholar
  3. Del Gatto A, Zaccaro L, Grieco P et al (2006) Novel and selective α(v)β3 receptor peptide antagonist: design, synthesis, and biological behavior. J Med Chem 49:3416–3420CrossRefPubMedGoogle Scholar
  4. Gasparini G, Brooks PC, Bingazoli E et al (1998) Vascular integrin α(v)β3: a new prognostic indicator in breast cancer. Clin Cancer Res 4:2625–2634PubMedGoogle Scholar
  5. Heppeler A, Froidevaux S, Eberle AN, Maecke HR (2000) Receptor targeting for tumor localisation and therapy with radiopeptides. Curr Med Chem 7:971–994PubMedGoogle Scholar
  6. Kaiser E, Colescott RL, Bossinger CD, Cook PI (1970) Colour test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem 34:595–598CrossRefPubMedGoogle Scholar
  7. Liapis H, Adler LM, Wick MR, Rader JS (1997) Expression of integrin α(v)β3 integrin is less frequent in ovarian epithelial tumors of low malignant potential in contrast to avarian carcinomas. Hum Pathol 28:443–449CrossRefPubMedGoogle Scholar
  8. Schnell O, Krebs B, Wagner E et al (2008) Expression of integrin αvβ3 in gliomas correlates with tumor grade and is not restricted to tumor vasculature. Brain Pathol 18:378–386CrossRefPubMedGoogle Scholar
  9. Sheppard RC, Williams BJ (1982) Acid-Labile resin linkage agents for use in solid-phase peptide-synthesis. Int J Pept Protein Res 20:451–454PubMedGoogle Scholar
  10. Zannetti A, Del Vecchio S, Iommelli F et al (2009) Imaging of αvβ3 expression by a bifunctional chimeric RGD peptide not cross-reacting with αvβ5. Clin Cancer Res 15:5224–5233CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Luca Monfregola
    • 1
  • Michele Saviano
    • 1
  • Stefania De Luca
    • 1
  1. 1.Istituto di Biostrutture e Bioimmagini IBB-CNRNaplesItaly

Personalised recommendations