Near-infrared optical imaging of ovarian cancer xenografts with novel alpha 3-integrin binding peptide "OA02".
Through screening of random one-bead one-compound (OBOC) libraries, we previously identified cyclic peptides with the cDGXGXXc motif that bind to alpha3 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 c-dGHCitGPQ-c ("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 (alpha3 integrin positive) and Raji (alpha3 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-alpha3 monoclonal antibody blocked the binding of this peptide to the ES-2 tumors.
Aina
Olulanu H
OH
University of California, Davis.
Marik
Jan
J
Gandour-Edwards
Regina
R
Lam
Kit S
KS
D000230:Adenocarcinoma / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D005260:Female; D006801:Humans; D039422:Integrin alpha3 / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011859:Radiography; D019265:Spectroscopy, Near-Infrared; D013194:Staining and Labeling; D014183:Transplantation, Heterologous
D039422:Integrin alpha3; D010455:Peptides