Nuclear Medicine and Biology
Volume 39, Issue 1 , Pages 23-34 , January 2012

Radioimmunotargeting of malignant glioma by monoclonal antibody D2C7 reactive against both wild-type and variant III mutant epidermal growth factor receptors

  • Michael R. Zalutsky

      Affiliations

    • Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 919 684 7708; fax: +1 919 684 7121.
    • ,
  • Abraham Boskovitz

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Chien-Tsun Kuan

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Charles N. Pegram

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Joanne Ayriss

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Carol J. Wikstrand

      Affiliations

    • Department of Microbiology, Saba University School of Medicine, Saba, Netherlands Antilles
    • ,
  • Anne F. Buckley

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Eric S. Lipp

      Affiliations

    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • James E. Herndon II

      Affiliations

    • Department of Biostatistics, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Roger E. McLendon

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Darell D. Bigner

      Affiliations

    • Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA

Received 7 April 2011 ,Revised 17 June 2011 ,Accepted 24 June 2011.

  • Image Result

    Determination of target specificity of MAbs for EGFRwt and EGFRvIII by flow cytometric analysis of EGFRwt-expressing NR6W cells (A), EGFRvIII-expressing NR6M cells (B), and EGFRwt- and EGFRvIII-negati

    Determination of target specificity of MAbs for EGFRwt and EGFRvIII by flow cytometric analysis of EGFRwt-expressing NR6W cells (A), EGFRvIII-expressing NR6M cells (B), and EGFRwt- and EGFRvIII-negative NR6 cells (C). Negative control antibody IgG2b (isotype of EGFR.1) or P588 IgG1 (isotype of L8A4 and D2C7) shown as gray-shaded area, compared to EGFRwt-specific EGFR.1 (black trace), EGFRvIII-specific L8A4 (black trace) and D2C7, which binds to both EGFRwt and EGFRvIII (gray trace).

  • Image Result
    Immunohistochemical analysis of binding of MAbs EGFR.1 (A), D2C7 (B) and L8A4 (C) to GBM tissue. Acetone-fixed frozen sections from patient with EGFRwt amplification stained with 5 μg of each MAb.

    Immunohistochemical analysis of binding of MAbs EGFR.1 (A), D2C7 (B) and L8A4 (C) to GBM tissue. Acetone-fixed frozen sections from patient with EGFRwt amplification stained with 5 μg of each MAb.

  • Image Result
    Cell-associated activity, internalization and processing of radiolabeled MAbs by EGFRwt-expressing WTT cells (left) and EGFRvIII-expressing NR6M cells (right). Shown are the percentages of radioiodine

    Cell-associated activity, internalization and processing of radiolabeled MAbs by EGFRwt-expressing WTT cells (left) and EGFRvIII-expressing NR6M cells (right). Shown are the percentages of radioiodine counts initially bound to the cells for 125I-labeled D2C7, 131I-labeled EGFR1 and 125I-labeled D2C7 that are cell associated (membrane+internalized), internalized and released degraded (TCA soluble) into the cell culture supernatant. Bars represent average of triplicate measurements±S.D.

☆ This study was supported by the following NIH grants: NINDS 5P50 NS20023, NCI CA42324, NCI 5P50 CA108786 and NCI R37 CA011898.

PII: S0969-8051(11)00153-3

doi: 10.1016/j.nucmedbio.2011.06.005

Nuclear Medicine and Biology
Volume 39, Issue 1 , Pages 23-34 , January 2012

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