This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reist, C. J. Articles by Zalutsky, M. R. Search for Related Content PubMed PubMed Citation Articles by Reist, C. J. Articles by Zalutsky, M. R.

Tumor-specific Anti-Epidermal Growth Factor Receptor Variant III Monoclonal Antibodies: Use of the Tyramine-Cellobiose Radioiodination Method Enhances Cellular Retention and Uptake in Tumor Xenografts¹

Departments of Pathology [C. J. R., G. E. A., S. N. K., C. J. W., D. D. B.] and Radiology [G. V., M. R. Z.] and Preuss Laboratory for Brain Tumor Research [D. D. B.], Duke University Medical Center, Durham, North Carolina 27710; Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107 [D. K. M., A. J. W.]; and Department of Pathology, Division of Research Pathology and Laboratory Medicine, Medical University of South Carolina, Charieston, South Carolina 29425 [M. C. W.]

Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene are characteristics of many types of tumors. One class of EGFR mutations, EGFRvIII, is characterized by an in-frame deletion resulting in a truncated external domain of the receptor. EGFR-vIII was first identified in a subset of gliomas and has since been found in some non-small cell lung carcinomas and breast carcinomas. mAbs specific for this variant form of EGFR but unreactive with the wild-type EGFR have been reported from our laboratory. This study further characterizes three of these antibodies. We determined, via radiolabeling techniques and immunofluorescence microscopy, that, after cell binding in vitro, the anti-EGFRvIII-specific mAbs internalize at 37°C. Furthermore, subsequent to internalization, the antibodies were processed intracelluarly, presumably by lysosomal degradation. We also examined the use of an alternative radiolabeling procedure that uses nonmetabolizable radioiodinated tyramine cellobiose. Our results show that the tyramine cellobiose labeling method allows for greater tumor cell retention of radiolabel in vitro (76% for tyramine cellobiose and 27% for Iodo-Gen after 24 h). Paired-label biodistribution studies in athymic mice indicate that anti-EGFRvIII mAb L8A4 localizes specifically to EGFRvIII-expressing tumor xenografts with a maximum of 34.3 ± 7.6% injected dose/g when labeled using tyramine collobiose compared with a maximum of 14.9 ± 4.3% injected dose/g using Iodo-Gen; similar results were obtained with mAb H10. These results suggest that the anti-EGFRvIII mAbs may serve as potential carriers for radioconjugate- and immunotoxin-based therapies for tumors expressing EGFRvIII.

¹ Supported in part by NIH Grants NS 20023, CA 56115, CA 11898, and CA 42324.

² To whom requests for reprints should be addressed, at Duke University Medical Center, Department of Radiology, Box 3808, Durham, NC 27710.

Received 5/22/95. Accepted 8/18/95.

This article has been cited by other articles:

				M. Aghi, K. S. Cohen, R. J. Klein, D. T. Scadden, and E. A. Chiocca Tumor Stromal-Derived Factor-1 Recruits Vascular Progenitors to Mitotic Neovasculature, where Microenvironment Influences Their Differentiated Phenotypes. Cancer Res., September 15, 2006; 66(18): 9054 - 9064. [Abstract] [Full Text] [PDF]

				K. N. Blehm, P. E. Spiess, J. E. Bondaruk, M. E. Dujka, G. J. Villares, Y.-j. Zhao, O. Bogler, K. D. Aldape, H. B. Grossman, L. Adam, et al. Mutations Within the Kinase Domain and Truncations of the Epidermal Growth Factor Receptor Are Rare Events in Bladder Cancer: Implications for Therapy Clin. Cancer Res., August 1, 2006; 12(15): 4671 - 4677. [Abstract] [Full Text] [PDF]

				W. Yang, R. F. Barth, G. Wu, S. Kawabata, T. J. Sferra, A. K. Bandyopadhyaya, W. Tjarks, A. K. Ferketich, M. L. Moeschberger, P. J. Binns, et al. Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4. Clin. Cancer Res., June 15, 2006; 12(12): 3792 - 3802. [Abstract] [Full Text] [PDF]

				C.-T. Kuan, K. Wakiya, J. M. Dowell, J. E. Herndon II, D. A. Reardon, M. W. Graner, G. J. Riggins, C. J. Wikstrand, and D. D. Bigner Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme. Clin. Cancer Res., April 1, 2006; 12(7): 1970 - 1982. [Abstract] [Full Text] [PDF]

				A. B. Heimberger, R. Hlatky, D. Suki, D. Yang, J. Weinberg, M. Gilbert, R. Sawaya, and K. Aldape Prognostic Effect of Epidermal Growth Factor Receptor and EGFRvIII in Glioblastoma Multiforme Patients Clin. Cancer Res., February 15, 2005; 11(4): 1462 - 1466. [Abstract] [Full Text] [PDF]

				C. A. Learn, T. L. Hartzell, C. J. Wikstrand, G. E. Archer, J. N. Rich, A. H. Friedman, H. S. Friedman, D. D. Bigner, and J. H. Sampson Resistance to Tyrosine Kinase Inhibition by Mutant Epidermal Growth Factor Receptor Variant III Contributes to the Neoplastic Phenotype of Glioblastoma Multiforme Clin. Cancer Res., May 1, 2004; 10(9): 3216 - 3224. [Abstract] [Full Text] [PDF]

				Z. Cheng, J. Chen, T. P. Quinn, and S. S. Jurisson Radioiodination of Rhenium Cyclized {alpha}-Melanocyte-Stimulating Hormone Resulting in Enhanced Radioactivity Localization and Retention in Melanoma Cancer Res., February 15, 2004; 64(4): 1411 - 1418. [Abstract] [Full Text] [PDF]

				M. Westphal, D. C. Hilt, E. Bortey, P. Delavault, R. Olivares, P. C. Warnke, I. R. Whittle, J. Jaaskelainen, and Z. Ram A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma Neuro-oncol, April 1, 2003; 5(2): 79 - 88. [Abstract] [PDF]

				R. B. Luwor, T. G. Johns, C. Murone, H-J. S. Huang, W. K. Cavenee, G. Ritter, L. J. Old, A. W. Burgess, and A. M. Scott Monoclonal Antibody 806 Inhibits the Growth of Tumor Xenografts Expressing Either the de2-7 or Amplified Epidermal Growth Factor Receptor (EGFR) but not Wild-Type EGFR Cancer Res., July 1, 2001; 61(14): 5355 - 5361. [Abstract] [Full Text] [PDF]

				R. Stein, S. V. Govindan, S. Chen, L. Reed, H. Richel, G. L. Griffiths, H. J. Hansen, and D. M. Goldenberg Radioimmunotherapy of a Human Lung Cancer Xenograft with Monoclonal Antibody RS7: Evaluation of 177Lu and Comparison of Its Efficacy with That of 90Y and Residualizing 131I J. Nucl. Med., June 1, 2001; 42(6): 967 - 974. [Abstract] [Full Text] [PDF]

				C. F. Foulon, C. J. Reist, D. D. Bigner, and M. R. Zalutsky Radioiodination via D-Amino Acid Peptide Enhances Cellular Retention and Tumor Xenograft Targeting of an Internalizing Anti-Epidermal Growth Factor Receptor Variant III Monoclonal Antibody Cancer Res., August 1, 2000; 60(16): 4453 - 4460. [Abstract] [Full Text]