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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 xenografts.

Publication ,  Journal Article
Reist, CJ; Archer, GE; Kurpad, SN; Wikstrand, CJ; Vaidyanathan, G; Willingham, MC; Moscatello, DK; Wong, AJ; Bigner, DD; Zalutsky, MR
Published in: Cancer Res
October 1, 1995

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. EGFRvIII 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 degrees C. Furthermore, subsequent to internalization, the antibodies were processed intracellularly, presumably by lysosomal degradation. We also examined the use of an alternative radiolabeling procedure that uses nonmetabolizable radio-iodinated 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 cellobiose 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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 1, 1995

Volume

55

Issue

19

Start / End Page

4375 / 4382

Location

United States

Related Subject Headings

  • Tyramine
  • Transplantation, Heterologous
  • Tissue Distribution
  • Radiation Dosage
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Neoplasm Transplantation
  • Microscopy, Fluorescence
  • Mice
  • Isotope Labeling
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Reist, C. J., Archer, G. E., Kurpad, S. N., Wikstrand, C. J., Vaidyanathan, G., Willingham, M. C., … Zalutsky, M. R. (1995). 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 xenografts. Cancer Res, 55(19), 4375–4382.
Reist, C. J., G. E. Archer, S. N. Kurpad, C. J. Wikstrand, G. Vaidyanathan, M. C. Willingham, D. K. Moscatello, A. J. Wong, D. D. Bigner, and M. R. Zalutsky. “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 xenografts.Cancer Res 55, no. 19 (October 1, 1995): 4375–82.
Reist CJ, Archer GE, Kurpad SN, Wikstrand CJ, Vaidyanathan G, Willingham MC, Moscatello DK, Wong AJ, Bigner DD, Zalutsky MR. 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 xenografts. Cancer Res. 1995 Oct 1;55(19):4375–4382.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 1, 1995

Volume

55

Issue

19

Start / End Page

4375 / 4382

Location

United States

Related Subject Headings

  • Tyramine
  • Transplantation, Heterologous
  • Tissue Distribution
  • Radiation Dosage
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Neoplasm Transplantation
  • Microscopy, Fluorescence
  • Mice
  • Isotope Labeling