Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas

Yukinari Kato, Ganesan Vaidyanathan, Mika Kato Kaneko, Kazuhiko Mishima, Nidhi Srivastava, Vidyalakshmi Chandramohan, Charles Pegram, Stephen T. Keir, Chien Tsun Kuan, Darell D. Bigner, Michael R. Zalutsky

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71 Citations (Scopus)

Abstract

Introduction: Podoplanin/aggrus is a mucin-like sialoglycoprotein that is highly expressed in malignant gliomas. Podoplanin has been reported to be a novel marker to enrich tumor-initiating cells, which are thought to resist conventional therapies and to be responsible for cancer relapse. The purpose of this study was to determine whether an anti-podoplanin antibody is suitable to target radionuclides to malignant gliomas. Methods: The binding affinity of an anti-podoplanin antibody, NZ-1 (rat IgG2a), was determined by surface plasmon resonance and Scatchard analysis. NZ-1 was radioiodinated with 125I using Iodogen [125I-NZ-1(Iodogen)] or N-succinimidyl 4-guanidinomethyl 3-[131I]iodobenzoate ([131I]SGMIB-NZ-1), and paired-label internalization assays of NZ-1 were performed. The tissue distribution of 125I-NZ-1(Iodogen) and that of [131I]SGMIB-NZ-1 were then compared in athymic mice bearing glioblastoma xenografts. Results: The dissociation constant (KD) of NZ-1 was determined to be 1.2×10-10 M by surface plasmon resonance and 9.8×10-10 M for D397MG glioblastoma cells by Scatchard analysis. Paired-label internalization assays in LN319 glioblastoma cells indicated that [131I]SGMIB-NZ-1 resulted in higher intracellular retention of radioactivity (26.3±0.8% of initially bound radioactivity at 8 h) compared to that from the 125I-NZ-1(Iodogen) (10.0±0.1% of initially bound radioactivity at 8 h). Likewise, tumor uptake of [131I]SGMIB-NZ-1 (39.9±8.8 %ID/g at 24 h) in athymic mice bearing D2159MG xenografts in vivo was significantly higher than that of 125I-NZ-1(Iodogen) (29.7±6.1 %ID/g at 24 h). Conclusions: The overall results suggest that an anti-podoplanin antibody NZ-1 warrants further evaluation for antibody-based therapy against glioblastoma.

Original languageEnglish
Pages (from-to)785-794
Number of pages10
JournalNuclear Medicine and Biology
Volume37
Issue number7
DOIs
Publication statusPublished - 2010 Oct
Externally publishedYes

Keywords

  • Biodistribution
  • Internalization
  • Malignant gliomas
  • Monoclonal antibody
  • Podoplanin
  • SGMIB

ASJC Scopus subject areas

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

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