Near-infrared optical imaging of ovarian cancer xenografts with novel α3-integrin binding peptide "OA02"

Olulanu H. Aina, Jan Marik, Regina F Gandour-Edwards, Kit Lam

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Through screening of random one-bead one-compound (OBOC) libraries, we previously identified cyclic peptides with the cDGXGXXc motif that bind to α3 integrin subunit on ovarian adenocarcinoma cell lines ES-2, SKOV-3, and CaOV-3. We subsequently synthesized two secondary libraries based on this motif and identified new peptides that bound with a higher affinity to these cell lines. One of the peptides identified from the 20% "down-substituted" focused library was the cdGHCit-GPQc ("OA02") peptide. The goal of this study was to determine whether this peptide labeled with near-infrared probes could be detected after intravenous injection in ovarian tumor-bearing mice and if it would selectively localize in the tumor. Three different forms of this peptide were synthesized, "OA02"-biotin (noncovalently linked to streptavidin-Cy5.5); "OA02"-Cy5.5 and "OA02"-AlexaFluo 680. Using a KODAK IS2000MM image station, these peptide probes were used at the near-infrared (NIR) spectra to image nude mice bearing ES-2 (α3 integrin positive) and Raji (α3 integrin negative) xenografts. The peptide probe displayed highly specific tumor uptake within 15 min, which lasted for 70 min for "OA02"Cy5.5 and "OA02"-AlexaFluo 680 and for 24 hours for "OA02"-biotin-streptavidin-Cy5.5. Some kidney and bladder signal were noted. Prior injection with anti-α3 monoclonal antibody blocked the binding of this peptide to the ES-2 tumors.

Original languageEnglish (US)
Pages (from-to)439-447
Number of pages9
JournalMolecular Imaging
Volume4
Issue number4
StatePublished - Oct 2005

Keywords

  • Combinatorial chemistry
  • Integrin
  • Optical imaging
  • Ovarian cancer
  • Peptides

ASJC Scopus subject areas

  • Engineering(all)

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