Nuclear Medicine and Biology
Volume 36, Issue 6 , Pages 659-669 , August 2009

Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of α-particle-emitting 211At-labeled trastuzumab

  • Abraham Boskovitz

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710 USA
  • ,
  • Roger E. McLendon

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710 USA
  • ,
  • Tatsunori Okamura

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710 USA
  • ,
  • John H. Sampson

      Affiliations

    • Department of Surgery, Duke University Medical Center, Durham, NC 27710 USA
  • ,
  • Darell D. Bigner

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710 USA
  • ,
  • Michael R. Zalutsky

      Affiliations

    • Department of Radiology, Duke University Medical Center, Durham, NC 27710 USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 919 684 7708; fax: +1 919 684 7121.

Received 28 January 2009 ,Revised 19 February 2009 ,Accepted 2 April 2009.

References 

  1. Prados MD. Primary neoplasms of the central nervous system in adults. In:  Kufe DW, et al. editor. Cancer medicine. 7th ed.. Hamilton, ON: BC Decker; 2006;p. 1037–1064
  2. Chamberlain MC. Neoplastic meningitis. J Clin Oncol. 2005;23:3605–3613
  3. Jaeckle KA. Neoplastic meningitis from systemic malignancies: diagnosis, prognosis and treatment. Semin Oncol. 2006;33:312–323
  4. Press MF, Cordon-Cardo C, Slamon DJ. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene. 1990;5:953–962
  5. Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res. 1990;50:4087–4091
  6. Natali PG, Nicotra MR, Bigotti A, et al. Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues. Int J Cancer. 1990;45:457–461
  7. Sliwkowski MX, Lofgren JA, Lewis GD, et al. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol. 1999;26:60–70
  8. Hortobagyi GN. Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. Semin Oncol. 2001;28:43–47
  9. Baselga J. Clinical trials of Herceptin (trastuzumab). Eur J Cancer. 2001;37(Suppl 1):S18–S24
  10. Pestalozzi BC, Brignoli S. Trastuzumab in CSF. J Clin Oncol. 2000;18:2349–2351
  11. Platini C, Long J, Walter S. Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab. Lancet Oncol. 2006;7:778–780
  12. Stemmler HJ, Schmitt M, Harbeck N, et al. Application of intrathecal trastuzumab (Herceptin) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer. Oncol Rep. 2006;15:1373–1377
  13. Laufman LR, Forsthoefel KF. Use of intrathecal trastuzumab in a patient with carcinomatous meningitis. Clin Breast Cancer. 2001;2:235
  14. Stemmler HJ, Mengele K, Schmitt M, et al. Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER-2 overexpressing metastatic breast cancer: a case report. Anticancer Drugs. 2008;19:832–836
  15. Mir O, Ropert S, Alexandre J, Lemare F, Goldwasser F. High dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2-expressing breast cancer. Annals Oncol. 2008;19:1978–1980
  16. Millar WT, Barrett A. Dosimetric model for antibody targeted radionuclide therapy of tumor cells in cerebrospinal fluid. Cancer Res. 1990;50(Suppl):1043s–1048s
  17. Vaidyanathan G, Zalutsky MR. Astatine radiopharmaceuticals: prospects and problems. Curr Radiopharm. 2008;1:177–196
  18. Zalutsky MR, Archer GE, Garg PK, Batra SK, Bigner DD. Chimeric anti-tenascin antibody 81C6: increased tumor localization compared with its murine parent. Nucl Med Biol. 1996;23:449–458
  19. Zalutsky MR, Zhao XG, Alston KL, Bigner D. High-level production of alpha-particle-emitting 211At and preparation of 211At-labeled antibodies for clinical use. J Nucl Med. 2001;42:1508–1515
  20. Benz CC, Scott GK, Sarup JC, et al. Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat. 1993;24:85–95
  21. Fuchs HE, Archer GE, Colvin OM, et al. Activity of intrathecal 4-hydroperoxycyclo-phosphamide in a nude rat model of human neoplastic meningitis. Cancer Res. 1990;50:1954–1959
  22. Grossi PM, Ochiai H, Archer GE, et al. Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer. Cancer Res. 2003;9:5514–5520
  23. Brown MT, Coleman E, Friedman AH, et al. Intrathecal 131I-labeled antitenascin monoclonal antibody 81C6 treatment of patients with leptomeningeal neoplasms or primary brain tumor resection cavities with subarachnoid communication: Phase I trial results. Clin Cancer Res. 1996;2:963–972
  24. Cokgor I, Akabani G, Friedman HS, et al. Long-term response in a patient with neoplastic meningitis secondary to melanoma treated with 131I-radiolabeled anti-chondroitin proteoglycan sulfate Me1-14 F(ab')2: a case study. Cancer. 2001;91:1809–1813
  25. Kramer K, Humm JL, Souweidane MM, et al. Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. J Clin Oncol. 2007;25:5465–5470
  26. Moseley RP, Benjamin JC, Ashpole RD, et al. Carcinomatous meningitis: antibody guided therapy with I-131 HMFG1. J Neurol Neurosurg Psychiatry. 1991;54:260–265
  27. Miederer M, McDevitt MR, Borchardt P, et al. Treatment of neuroblastoma meningeal carcinomatosis with intrathecal application of α-emitting atomic nanogenerators targeting disialo-ganglioside GD2. Clin Cancer Res. 2004;10:6985–6992
  28. Akabani G, Carlin S, Welsh P, Zalutsky MR. In vitro cytotoxicity of 211At-labeled trastuzumab in human breast cancer cell lines: effect of specific activity and HER2 receptor heterogeneity on survival fraction. Nucl Med Biol. 2006;33:333–347
  29. Braun S, Hepp F, Sommer HL, Pantel K. Tumor-antigen heterogeneity of disseminated breast cancer cells: implications for immunotherapy of minimal residual disease. Int J Cancer. 1999;84:1–5
  30. Bergman I, Burckart GJ, Pohl CR, et al. Pharmacokinetics of IgG and IgM anti-ganglioside antibodies in rats and monkeys after intrathecal administration. J Pharmacol Exp Ther. 1998;284:111–115
  31. Zalutsky MR, McLendon RE, Garg PK, Archer GE, Schuster JM, Bigner DD. Radioimmunotherapy of neoplastic meningitis in rats using an α-particle-emitting immunoconjugate. Cancer Res. 1994;54:4719–4725
  32. van den Berg MP, Romeijn SG, Verhoef JC, Merkus FWHM. Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity. J Neurosci Methods. 2002;116:99–107
  33. Nopoulos P, Flaum M, Andreasen NC. Sex differences in brain morphology in schizophrenia. Am J Psychiatry. 1997;154:1648–1654
  34. McLendon RE, Archer GE, Larsen RH, Akabani G, Bigner DD, Zalutsky MR. Radiotoxicity of systemically administered 211At-labeled human/mouse chimeric monoclonal antibody: a long-term survival study with histological analysis. Int J Radiat Oncol Biol Phys. 1999;45:491–499
  35. Zalutsky MR, Reardon DA, Akabani G, et al. Clinical experience with α-emitting astatine-211: treatment of recurrent brain tumor patients with 211At-labeled chimeric 81C6 anti-tenascin monoclonal antibody. J Nucl Med. 2008;49:30–38
  36. Olafsen T, Kenanova VE, Sundaresan G, et al. Optimizing radiolabeled engineered anti-p185HER2 antibody fragments for in vivo imaging. Cancer Res. 2005;65:5907–5916
  37. Vaidyanathan G, Affleck DJ, Bigner DD, Zalutsky MR. N-succinimidyl 3-[211At]astato-4-guanidinomethylbenzoate: an acylation agent for labeling internalizing antibodies with α-particle emitting 211At. Nucl Med Biol. 2003;30:351–359

 This work was supported by Grants CA42324 and NS20023 from the National Institutes of Health and Grant DOE-FG02-08ER64697 from the Department of Energy.

PII: S0969-8051(09)00087-0

doi: 10.1016/j.nucmedbio.2009.04.003

Nuclear Medicine and Biology
Volume 36, Issue 6 , Pages 659-669 , August 2009