Near-infrared optical imaging in glioblastoma xenograft with ligand-targeting α3 integrin

  • Wenwu Xiao
  • Nianhuan Yao
  • Li Peng
  • Ruiwu Liu
  • Kit S. LamEmail author
Original Article



Patients with glioblastoma usually have a very poor prognosis. Even with a combination of radiotherapy plus temozolomide, the median survival of these patients is only 14.6 months. New treatment approaches to this cancer are needed. Our purpose is to develop new cell surface-binding ligands for glioblastoma cells and use them as targeted imaging and therapeutic agents for this deadly disease.


One-bead one-compound combinatorial cyclic peptide libraries were screened with live human glioblastoma U-87MG cells. The binding affinity and targeting specificity of peptides identified were tested with in vitro experiments on cells and in vivo and ex vivo experiments on U-87MG xenograft mouse model.


A cyclic peptide, LXY1, was identified and shown to be binding to the α3 integrin of U-87MG cells with moderately high affinity (K d = 0.5 ± 0.1 μM) and high specificity. Biotinylated LXY1, when complexed with streptavidin–Cy5.5 (SA–Cy5.5) conjugate, targeted both subcutaneous and orthotopic U-87MG xenograft implants in nude mice. The in vivo targeting specificity was further verified by strong inhibition of tumor uptake of LXY1–biotin–SA–Cy5.5 complex when intravenously injecting the animals with anti-α3 integrin antibody or excess unlabeled LXY1 prior to administrating the imaging probe. The smaller univalent LXY1–Cy5.5 conjugate (2,279 Da) was found to have a faster accumulation in the U-87MG tumor and shorter retention time compared with the larger tetravalent LXY1–biotin–SA–Cy5.5 complex (approximately 64 kDa).


Collectively, the data reveals that LXY1 has the potential to be developed into an effective imaging and therapeutic targeting agent for human glioblastoma.


Combinatorial chemistry One-bead one-compound peptide library Integrin Cancer targeting Glioblastoma Optical imaging Molecular imaging Small animal imaging 







random amino acids








trifluoroacetic acid




ethylenediaminetetraacetic acid






Institutional Animal Care and Use Committee


fetal bovine serum


phosphate-buffered saline



This work was supported by the National Institutes of Health (R33CA-86364, R33CA-99136, U19CA113298, and P50CA097257). We would like to thank Ms. Mary Saunders and Mr. Joel Kugelmass for the editorial assistance.

Conflict of interest

There is no conflict of interest for this manuscript.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Wenwu Xiao
    • 1
  • Nianhuan Yao
    • 1
  • Li Peng
    • 1
  • Ruiwu Liu
    • 1
  • Kit S. Lam
    • 1
    Email author
  1. 1.Division of Hematology and Oncology, Department of Internal Medicine, UC Davis Cancer CenterUniversity of California DavisSacramentoUSA

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