Skip to main content
Journal cover image

Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of alpha-particle-emitting (211)At-labeled trastuzumab.

Publication ,  Journal Article
Boskovitz, A; McLendon, RE; Okamura, T; Sampson, JH; Bigner, DD; Zalutsky, MR
Published in: Nucl Med Biol
August 2009

INTRODUCTION: Carcinomatous meningitis (CM) is a devastating disease characterized by the dissemination of malignant tumor cells into the subarachnoid space along the brain and spine. Systemic treatment with monoclonal antibody (mAb) trastuzumab can be effective against HER2-positive systemic breast carcinoma but, like other therapies, is ineffective against CM. The goal of this study was to evaluate the therapeutic effect of alpha-particle emitting (211)At-labeled trastuzumab following intrathecal administration in a rat model of breast carcinoma CM. METHODS: Athymic rats were injected intrathecally with MCF-7/HER2-18 breast carcinoma cells through a surgically implanted indwelling intrathecal catheter. In Experiment 1, animals received 33 or 66 muCi (211)At-labeled trastuzumab, cold trastuzumab or saline. In Experiment 2, animals were inoculated with a lower tumor burden and received 46 or 92 muCi (211)At-labeled trastuzumab or saline. In Experiment 3, animals received 28 muCi (211)At-labeled trastuzumab, 30 muCi (211)At-labeled TPS3.2 control mAb or saline. Histopathological analysis of the neuroaxis was performed at the end of the study. RESULTS: In Experiment 1, median survival increased from 21 days for the saline and cold trastuzumab groups to 45 and 48 days for 33 and 66 muCi (211)At-labeled trastuzumab, respectively. In Experiment 2, median survival increased from 23 days for saline controls to 68 and 92 days for 46 and 92 muCi (211)At-labeled trastuzumab, respectively. In Experiment 3, median survival increased from 20 days to 29 and 36 days for animals treated with (211)At-labeled TPS3.2 and (211)At-labeled trastuzumab, respectively. Long-term survivors were observed exclusively in the (211)At-trastuzumab-treated groups. CONCLUSION: Intrathecal (211)At-labeled trastuzumab shows promise as a treatment for patients with HER2-positive breast CM.

Duke Scholars

Published In

Nucl Med Biol

DOI

EISSN

1872-9614

Publication Date

August 2009

Volume

36

Issue

6

Start / End Page

659 / 669

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Trastuzumab
  • Survival Rate
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Rats
  • Radioimmunotherapy
  • Nuclear Medicine & Medical Imaging
  • Mice
  • Meningeal Carcinomatosis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Boskovitz, A., McLendon, R. E., Okamura, T., Sampson, J. H., Bigner, D. D., & Zalutsky, M. R. (2009). Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of alpha-particle-emitting (211)At-labeled trastuzumab. Nucl Med Biol, 36(6), 659–669. https://doi.org/10.1016/j.nucmedbio.2009.04.003
Boskovitz, Abraham, Roger E. McLendon, Tatsunori Okamura, John H. Sampson, Darell D. Bigner, and Michael R. Zalutsky. “Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of alpha-particle-emitting (211)At-labeled trastuzumab.Nucl Med Biol 36, no. 6 (August 2009): 659–69. https://doi.org/10.1016/j.nucmedbio.2009.04.003.
Boskovitz A, McLendon RE, Okamura T, Sampson JH, Bigner DD, Zalutsky MR. Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of alpha-particle-emitting (211)At-labeled trastuzumab. Nucl Med Biol. 2009 Aug;36(6):659–69.
Boskovitz, Abraham, et al. “Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of alpha-particle-emitting (211)At-labeled trastuzumab.Nucl Med Biol, vol. 36, no. 6, Aug. 2009, pp. 659–69. Pubmed, doi:10.1016/j.nucmedbio.2009.04.003.
Boskovitz A, McLendon RE, Okamura T, Sampson JH, Bigner DD, Zalutsky MR. Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of alpha-particle-emitting (211)At-labeled trastuzumab. Nucl Med Biol. 2009 Aug;36(6):659–669.
Journal cover image

Published In

Nucl Med Biol

DOI

EISSN

1872-9614

Publication Date

August 2009

Volume

36

Issue

6

Start / End Page

659 / 669

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Trastuzumab
  • Survival Rate
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Rats
  • Radioimmunotherapy
  • Nuclear Medicine & Medical Imaging
  • Mice
  • Meningeal Carcinomatosis