Effect of blood-brain barrier disruption on intact and fragmented monoclonal antibody localization in intracerebral lung carcinoma xenografts

E. A. Neuwelt, P. A. Barnett, K. E. Hellstrom, I. Hellstrom, C. I. McCormick, F. L. Ramsey

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

These studies highlight several factors that affect monoclonal antibody (Mab) localization to a tumor in the brain, including tumor permeability, nonspecific and specific binding, plasma half-life, radiolabeled antibody stability and the blood-brain barrier. Methods: A pancarcinoma Mab [L6 IgG, F(ab')2 and Fab] and an irrelevant isotype-matched antibody [P1.17 IgG and F(ab')2] were given with and without osmotic blood-brain barrier disruption in a LX-1 human small-cell lung carcinoma intracerebral xenograft model. Results: Intracerebral tumor size and permeability to antibody increased with the selection of 10, 14 or 17 days postinoculation when antibody was administered. Barrier disruption increased the delivery, particularly at earlier time points, which was dependent on antibody-specific and nonspecific binding and tumor permeability. Dehalogenation and/or antibody binding stability also appeared to affect the percent delivery. Conclusion: These studies demonstrate important variables that should be considered when clinical trials are designed or Mab delivery and localization in intracerebral tumor models are evaluated.

Original languageEnglish (US)
Pages (from-to)1831-1841
Number of pages11
JournalJournal of Nuclear Medicine
Volume35
Issue number11
StatePublished - Jan 1 1994

Keywords

  • blood-brain barrier
  • monoclonal antibody
  • xenografts

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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