Imaging of αvβ3 expression by a bifunctional chimeric RGD peptide not cross-reacting with α vβ5

Antonella Zannetti, Silvana Del Vecchio, Francesca Iommelli, Annarita Del Gatto, Stefania De Luca, Laura Zaccaro, Angela Papaccioli, Jvana Sommella, Mariarosaria Panico, Antonio Speranza, Paolo Grieco, Ettore Novellino, Michele Saviano, Carlo Pedone, Marco Salvatore

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To test whether a novel bifunctional chimeric peptide comprising a cyclic Arg-Gly-Asp pentapeptide covalently bound to an echistatin domain can discriminate αvβ3 from α vβ5 integrin, thus allowing the in vivo selective visualization of αvβ3 expression by single-photon and positron emission tomography (PET) imaging. Experimental Design: The chimeric peptide was preliminarily tested for inhibition of αvβ3-dependent cell adhesion and competition of 125I-echistatin binding to membrane of stably transfected K562 cells expressing αvβ3 (Kαvλ 3) or αvβ5 (Kα vβ5) integrin. The chimeric peptide was then conjugated with diethylenetriaminepentaacetic acid and labeled with 111In for single-photon imaging, whereas a one-step procedure was used for labeling the full-length peptide and a truncated derivative, lacking the last five C-terminal amino acids, with 18F for PET imaging. Nude mice bearing tumors from Kαvβ3, Kαvβ5, U87MG human glioblastoma, and A431 human epidermoid cells were subjected to single-photon and PET imaging. Results: Adhesion and competitive binding assays showed that the novel chimeric peptide selectively binds to αvβ3 integrin and does not cross-react with αvβ5. In agreement with in vitro findings, single-photon and PET imaging studies showed that the radiolabeled chimeric peptide selectively localizes in tumor xenografts expressing αvβ3 and fails to accumulate in those expressing αvβ5 integrin. When 18F-labeled truncated derivative was used for PET imaging, αvβ3- and αvβ 5-expressing tumors were visualized, indicating that the five C-terminal amino acids are required to differentially bind the two integrins. Conclusion: Our findings indicate that the novel chimeric Arg-Gly-Asp peptide, having no cross-reaction with αvβ5 integrin, allows highly selective αvβ3 expression imaging and monitoring.

Original languageEnglish
Pages (from-to)5224-5233
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number16
DOIs
Publication statusPublished - Aug 15 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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