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

Nucl Med Biol. 2010 Oct;37(7):785-94. doi: 10.1016/j.nucmedbio.2010.03.010.


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 IgG(2a)), was determined by surface plasmon resonance and Scatchard analysis. NZ-1 was radioiodinated with (125)I using Iodogen [(125)I-NZ-1(Iodogen)] or N-succinimidyl 4-guanidinomethyl 3-[(131)I]iodobenzoate ([(131)I]SGMIB-NZ-1), and paired-label internalization assays of NZ-1 were performed. The tissue distribution of (125)I-NZ-1(Iodogen) and that of [(131)I]SGMIB-NZ-1 were then compared in athymic mice bearing glioblastoma xenografts.

Results: The dissociation constant (K(D)) 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 [(131)I]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 (125)I-NZ-1(Iodogen) (10.0 ± 0.1% of initially bound radioactivity at 8 h). Likewise, tumor uptake of [(131)I]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 (125)I-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.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / therapeutic use*
  • Antibodies, Monoclonal / immunology*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Female
  • Flow Cytometry
  • Glioblastoma / immunology
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Iodine Radioisotopes / pharmacokinetics
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Radioimmunotherapy*
  • Radiopharmaceuticals / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Surface Plasmon Resonance
  • Tissue Distribution


  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Pdpn protein, rat
  • Radiopharmaceuticals