In vitro and in vivo behavior of radiolabeled chimeric anti-EGFRvIII monoclonal antibody: comparison with its murine parent.

Published

Journal Article

The mutant version of the epidermal growth factor receptor EGFRvIII has been found on gliomas and other tumors, but not on normal tissues. Radioiodinated murine (mu) L8A4 monoclonal antibody (MAb) specifically targets EGFRvIII xenografts in vivo when labeled using N-succinimidyl 5-iodo-3-pyridinecarboxylate (SIPC). A chimeric (ch) MAb consisting of the variable region of muL8A4 and the constant domains of human IgG2 has been developed that has an affinity and radioiodinated immunoreactive fraction comparable to muL8A4. In vitro, both MAbs were internalized and processed by EGFRvIII expressing cell lines (U87MG delta EGFR or NR6M) at similar rates (maximum intracellular retention, 35-40%). In paired-label tissue distribution studies in athymic mice bearing U87MG delta EGFR tumor xenografts, the ch:mu L8A4 uptake ratio in normal tissues rose to greater than 2:1, whereas in tumor, the ratio remained 1:1 throughout the experiment. These results indicate that chL8A4 exhibits similar binding and internalization properties as its murine parent, but suggest different intracellular processing and/or deposition of catabolites in normal tissues for chL8A4.

Full Text

Duke Authors

Cited Authors

  • Reist, CJ; Batra, SK; Pegram, CN; Bigner, DD; Zalutsky, MR

Published Date

  • October 1997

Published In

Volume / Issue

  • 24 / 7

Start / End Page

  • 639 - 647

PubMed ID

  • 9352535

Pubmed Central ID

  • 9352535

Electronic International Standard Serial Number (EISSN)

  • 1872-9614

International Standard Serial Number (ISSN)

  • 0969-8051

Digital Object Identifier (DOI)

  • 10.1016/s0969-8051(97)00080-2

Language

  • eng