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  • Integrin αvβ3-Targeted IRDye 800CW Near-Infrared Imaging of Glioblastoma

    Author(s)
    Huang, Ruimin
    Vider, Jelena
    Kovar, Joy L
    Olive, D Michael
    Mellinghoff, Ingo K
    Mayer-Kuckuk, Philipp
    Kircher, Moritz F
    Blasberg, Ronald G
    Griffith University Author(s)
    Vider, Jelena
    Year published
    2012
    Metadata
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    Abstract
    Purpose: Integrin avb3 plays an important role in tumor angiogenesis, growth, and metastasis. We have tested a targeted probe to visualize integrin receptor expression in glioblastomas using near-infrared fluorescent (NIRF) imaging. Experimental design: A transgenic glioblastoma mouse model (RCAS-PDGF-driven/tv-a glioblastoma, which mimics the infiltrative growth pattern of human glioblastomas) and two human orthotopic glioblastoma models (U-87MGwith high integrin b3 expression and TS543 with low integrin b3 expression) were studied. An integrin-targeting NIRF probe, IRDye 800CW-cyclic-RGD peptide (IRDye 800CW-RGD), ...
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    Purpose: Integrin avb3 plays an important role in tumor angiogenesis, growth, and metastasis. We have tested a targeted probe to visualize integrin receptor expression in glioblastomas using near-infrared fluorescent (NIRF) imaging. Experimental design: A transgenic glioblastoma mouse model (RCAS-PDGF-driven/tv-a glioblastoma, which mimics the infiltrative growth pattern of human glioblastomas) and two human orthotopic glioblastoma models (U-87MGwith high integrin b3 expression and TS543 with low integrin b3 expression) were studied. An integrin-targeting NIRF probe, IRDye 800CW-cyclic-RGD peptide (IRDye 800CW-RGD), was tested by in vivo and ex vivo NIRF imaging. Results: We show that the IRDye 800CW-RGD peptide: (i) specifically binds to integrin receptors; (ii) is selectively localized to glioblastoma tissue with overexpressed integrin receptors and is retained over prolonged periods of time; (iii) is associated with minimal autofluorescence and photobleaching because of imaging at 800 nm; (iv) provides delineation of tumor tissue with high precision because of a high tumor-tonormal brain fluorescence ratio (79.7 6.9, 31.2 2.8, and 16.3 1.3) in the U-87 MG, RCAS-PDGF, and TS543 models, respectively; P < 0.01); and (v) enables fluorescence-guided glioblastoma resection. Importantly, small foci of residual fluorescence were observed after resection was completed using white light imaging alone, and these fluorescent foci were shown to represent residual tumor tissue by histology. Conclusions: NIRF imaging with the IRDye 800CW-RGD probe provides a simple, rapid, low-cost, nonradioactive, and highly translatable approach for improved intraoperative glioblastoma visualization and resection. It also has the potential to serve as an imaging platform for noninvasive cancer detection and drug efficacy evaluation studies.
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    Journal Title
    Clinical Cancer Research
    Volume
    18
    Issue
    20
    DOI
    https://doi.org/10.1158/1078-0432.CCR-12-0374
    Subject
    Cancer Cell Biology
    Oncology and Carcinogenesis
    Publication URI
    http://hdl.handle.net/10072/53053
    Collection
    • Journal articles

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