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

Craig J. Reist, Surinder K. Batra, Charles N. Pegram, Darell D. Bigner, Michael R. Zalutsky

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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-pyrldinecarboxylate (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 EGFRvlII expressing cell lines (U87MGΔEGFR or NR6M) at similar rates (maximum intracellular retention, 35-40%). In paired-label tissue distribution studies in athymic mice bearing U87MGΔEGFR 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.

Original languageEnglish (US)
Pages (from-to)639-647
Number of pages9
JournalNuclear Medicine and Biology
Volume24
Issue number7
DOIs
StatePublished - Oct 1997

Keywords

  • Chimeric
  • EGFRvIII
  • Internalization
  • Monoclonal antibodies
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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