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

Publication ,  Journal Article
Kato, Y; Vaidyanathan, G; Kaneko, MK; Mishima, K; Srivastava, N; Chandramohan, V; Pegram, C; Keir, ST; Kuan, C-T; Bigner, DD; Zalutsky, MR
Published in: Nucl Med Biol
October 2010

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.

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Published In

Nucl Med Biol

DOI

EISSN

1872-9614

Publication Date

October 2010

Volume

37

Issue

7

Start / End Page

785 / 794

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Surface Plasmon Resonance
  • Rats, Sprague-Dawley
  • Rats
  • Radiopharmaceuticals
  • Radioimmunotherapy
  • Nuclear Medicine & Medical Imaging
  • Mice, Inbred BALB C
  • Mice
  • Membrane Glycoproteins
 

Citation

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MLA
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Kato, Y., Vaidyanathan, G., Kaneko, M. K., Mishima, K., Srivastava, N., Chandramohan, V., … Zalutsky, M. R. (2010). Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas. Nucl Med Biol, 37(7), 785–794. https://doi.org/10.1016/j.nucmedbio.2010.03.010
Kato, Yukinari, Ganesan Vaidyanathan, Mika Kato Kaneko, Kazuhiko Mishima, Nidhi Srivastava, Vidyalakshmi Chandramohan, Charles Pegram, et al. “Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas.Nucl Med Biol 37, no. 7 (October 2010): 785–94. https://doi.org/10.1016/j.nucmedbio.2010.03.010.
Kato Y, Vaidyanathan G, Kaneko MK, Mishima K, Srivastava N, Chandramohan V, et al. Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas. Nucl Med Biol. 2010 Oct;37(7):785–94.
Kato, Yukinari, et al. “Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas.Nucl Med Biol, vol. 37, no. 7, Oct. 2010, pp. 785–94. Pubmed, doi:10.1016/j.nucmedbio.2010.03.010.
Kato Y, Vaidyanathan G, Kaneko MK, Mishima K, Srivastava N, Chandramohan V, Pegram C, Keir ST, Kuan C-T, Bigner DD, Zalutsky MR. Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas. Nucl Med Biol. 2010 Oct;37(7):785–794.
Journal cover image

Published In

Nucl Med Biol

DOI

EISSN

1872-9614

Publication Date

October 2010

Volume

37

Issue

7

Start / End Page

785 / 794

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Surface Plasmon Resonance
  • Rats, Sprague-Dawley
  • Rats
  • Radiopharmaceuticals
  • Radioimmunotherapy
  • Nuclear Medicine & Medical Imaging
  • Mice, Inbred BALB C
  • Mice
  • Membrane Glycoproteins