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Molecular imaging of breast tumors using a near-infrared fluorescently labeled clusterin binding peptide.
MedLine Citation:
PMID:  22119929     Owner:  NLM     Status:  Publisher    
Several reports have shown that secreted clusterin (sCLU) plays multiple roles in tumor development and metastasis. Here, we report on a 12-mer sCLU binding peptide (designated P3378) that was identified by screening a phage-display peptide library against purified human sCLU. Differential resonance perturbation (DRP) nuclear magnetic resonance (NMR) using P3378 and a scrambled control peptide (designated P3378R) confirmed the P3378-sCLU interaction and demonstrated that it was sequence specific. P3378 and P3378R peptides were conjugated to an Alexa680 near infrared fluorophore (NIRF) and assessed for their tumor homing abilities in in vivo time-domain fluorescence optical imaging experiments using living 4T1 tumor bearing BALB/c mice. When injected in separate animals, both peptides accumulated at the tumor site, however the NIRF-labeled P3378 peptide was retained for a significant longer period of time than the P3378R peptide. Similar observations were made after simultaneously injecting the same tumor-bearing animal with a peptide mixture of P3378 DyLight (DL)680 and the P3378R-DL800. Co-injection of P3378-DL680 with excess unlabeled P3378 blocked tumor accumulation of fluorescent signal while excess P3378R control peptide did not confirming the sequence specificity of the tumor accumulation. Finally, ex vivo fluorescence microscopy of these tumors confirmed the presence of P3378-DL680 in the tumor and its colocalization with CLU. These results confirm the tumor targeting specificity of the P3378 CLU-binding peptide and suggest its usefulness for the in vivo monitoring of solid tumors secreting detectable levels of CLU. © 2011 Wiley-Liss, Inc.
Rana Filfil; Béatrice Paul-Roc; Christiane Cantin; Umar Iqbal; Dmitri Tolkatchev; Anna Vinogradova; Ping Xu; Feng Ni; Maureen D O'Connor-McCourt; Anne Eg Lenferink
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-28
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Receptors, Signaling and Proteomics Group, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal (Quebec) Canada H4P 2R2; Bio-NMR and Protein Research Group, Biotechnology Research Institute, 1200 Montreal Road, M-54, Ottawa, Ontario, K1A 0R6, Canada.
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