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Radioimmunotherapy in Brain Tumors

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Abstract

Gliomas and meningiomas are the most frequent primary brain tumors. Surgery, external beam radiotherapy, and chemotherapy are, at present, the essential components in the therapeutic management of malignant brain masses. Nevertheless, these methods present limitations in terms of clinical response and rate of toxicity and morbidity. Because of the need for complementary or alternative treatment modalities, brain tumor cells have been persistently investigated to determine the presence of specific antigens, with the goal of produce\ing antibodies that might be useful as therapeutics.

An emerging approach is targeted radiotherapy, a strategy that utilizes a molecular vehicle (antibody or peptide) to selectively deliver cytotoxic radiation emitted by a radionuclide to malignant cell populations. Although many types of labeled molecules have been investigated for targeted cancer radiotherapy, trials in brain tumors have almost exclusively exploited the potential of radioimmunotherapy (RIT) by employing a radiolabeled monoclonal antibodies (MoAbs) as targeting vehicle. Recently, somatostatin receptors have been shown to be overexpressed in various brain tumors, especially meningiomas and glia-derived tumors. This evidence, following the clinical experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors, has suggested that somatostatin analogs, coupled with appropriate radioisotopes, might also be of value in the treatment of brain tumors.

The most commonly used radionuclides in targeted radiotherapy are beta-emitters, specifically: Yttrium-90 (90Y), Iodine-131 (131I), and Lutetium-177 (177Lu). The differences in physical half-life, the presence or absence of gamma rays, the energy, and consequently, the range of beta-particles in tissue are important variables with respect to the radiation dose that can be delivered to the tumor.

Although targeted radiotherapy models have been principally evaluated for systemic administration, RIT and PRRT may also be applied loco-regionally, in order to reduce systemic toxicity.

This chapter describes systemic and intracavitary use of RIT in high grade glioma. A brief report on PRRT in meningioma is also included.

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References

  1. Davis FG, Preston-Martin S. Epidemiology, incidence and survival in central nervous system neoplasia. In: Bigner DD, McLendon RE, Bruner JM, editors. Russell and Rubinstein’s pathology of tumors of the nervous system. 6th ed. London: Arnold; 1998. p. 5–145.

    Google Scholar 

  2. Stewart LA. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 2002;359(9311):1011–8.

    Article  PubMed  CAS  Google Scholar 

  3. Wong ET, Hess KR, Gleason MJ, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol. 1999;17(8): 2572–8.

    PubMed  CAS  Google Scholar 

  4. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2): 97–109.

    Article  PubMed  Google Scholar 

  5. Maher EA, Furnari FB, Bachoo RM, et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev. 2001;15(11):1311–33.

    Article  PubMed  CAS  Google Scholar 

  6. Kleihues P, Burger PC, Scheithauer BW. The new WHO classification of brain tumours. Brain Pathol. 1993;3(3):255–68.

    Article  PubMed  CAS  Google Scholar 

  7. Zülch KJ, editor. Histological typing of tumours of the central nervous system. Geneva: World Health Organization; 1979.

    Google Scholar 

  8. Jackson RJ, Fuller GN, Abi-Said D, et al. Limitations of stereotactic biopsy in the initial management of gliomas. Neuro Oncol. 2001;3(3):193–200.

    PubMed  CAS  Google Scholar 

  9. Perry A, Jenkins RB, O’Fallon JR, et al. Clinicopathologic study of 85 similarly treated patients with anaplastic astrocytic tumors. An analysis of DNA content (ploidy), cellular proliferation, and p53 expression. Cancer. 1999;86(4):672–83.

    Article  PubMed  CAS  Google Scholar 

  10. Barker 2nd FG, Chang SM, Larson DA, et al. Age and radiation response in glioblastoma multiforme. Neurosurgery. 2001;49(6):1288–98.

    Article  PubMed  Google Scholar 

  11. Vuorinen V, Hinkka S, Färkkilä M, Jääskeläinen J. Debulking or biopsy of malignant glioma in elderly people—a randomised study. Acta Neurochir (Wien). 2003;145(1):5–10.

    Article  CAS  Google Scholar 

  12. Keles GE, Lamborn KR, Berger MS. Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome. J Neurosurg. 2001;95(5):735–45.

    Article  PubMed  CAS  Google Scholar 

  13. Hess KR. Extent of resection as a prognostic variable in the treatment of gliomas. J Neurooncol. 1999;42(3): 227–31.

    Article  PubMed  CAS  Google Scholar 

  14. Stupp R, Dietrich P-Y, Ostermann Kraljevic S, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol. 2002;20(5):1375–82.

    Article  PubMed  CAS  Google Scholar 

  15. Stupp R, Hegi ME, Mason WP, et al.; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–66.

    Google Scholar 

  16. Leibel SA, Gutin PH, Wara WM, et al. Survival and quality of life after interstitial implantation of removable high-activity iodine-125 sources for the treatment of patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 1989;17(6):1129–39.

    Article  PubMed  CAS  Google Scholar 

  17. Shrieve DC, Alexander E, Wen PY, et al. Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme. Neurosurgery. 1995;36(2):275–84.

    Article  PubMed  CAS  Google Scholar 

  18. Greig NH, Yu QS, Utsuki T, et al. Optimizing drugs for brain action. In: Koliber D, Lustig S, Shapira S, editors. Blood–brain barrier drug delivery and brain pathology. New York: Kluwer Academic/Plenum; 2001.

    Google Scholar 

  19. Brem H, Mahaley Jr MS, Vick NA, Black KL, Schold Jr SC, Burger PC, Friedman AH, Ciric IS, Eller TW, Cozzens JW, et al. Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. J Neurosurg. 1991;74(3):441–6.

    Article  PubMed  CAS  Google Scholar 

  20. Strasser JF, Fung LK, Eller S, Grossman SA, Saltzman WM. Distribution of 1,3-bis(2-chloroethyl)-1-­nitrosourea and tracers in the rabbit brain after interstitial delivery by biodegradable polymer implants. J Pharmacol Exp Ther. 1995;275(3):1647–55.

    PubMed  CAS  Google Scholar 

  21. Clark AS, Deans B, Stevens MF, et al. Antitumor imidazotetrazines: 32. Synthesis of novel imidazotetrazinones and related dicyclic heterocycles to probe the mode of action on the antitumor drug temozolomide. J Med Chem. 1995;38(9):1493–504.

    Article  PubMed  CAS  Google Scholar 

  22. Esteller M, Gargia-Foncillas J, Andion E, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343(19):1350–4.

    Article  PubMed  CAS  Google Scholar 

  23. Brem S, Cotran R, Folkman J. Tumor angiogenesis: a quantitative method for histologic grading. J Natl Cancer Inst. 1972;48(2):347–56.

    PubMed  CAS  Google Scholar 

  24. Salmaggi A, Eoli M, Frigerio S, et al. Intracavitary VEGF, bFGF, IL-8, IL-12 levels in primary and recurrent malignant glioma. J Neurooncol. 2003;62(3): 297–303.

    Article  PubMed  Google Scholar 

  25. Leon SP, Folkerth RD, Black PM. Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer. 1996;77(2):362–72.

    Article  PubMed  CAS  Google Scholar 

  26. Zhou YH, Tan F, Hess KR, Yung WK. The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival. Clin Cancer Res. 2003;9(9):3369–75.

    PubMed  CAS  Google Scholar 

  27. Fine HA, Figg WD, Jaeckle K, et al. Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol. 2000; 18(4):708–15.

    PubMed  CAS  Google Scholar 

  28. Drappatz J, Wong ET, Schiff D, et al. A pilot safety study of lenalidomide and radiotherapy for patients with newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2009;73(1):222–7.

    Article  PubMed  CAS  Google Scholar 

  29. National Comprehensive Cancer Network. NCCN practice guidelines in oncology: central nervous system cancers. v.1.2008. Fort Washington: National Comprehensive Cancer Network; 2009. Available from URL: http://www.nccn.org/professionals/physician_gls/PDF/cns.pdf. Accessed 21 May 2009.

  30. Cohen M, Shen Y, Keegan P, et al. FDA approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009; 14(11):1131–8.

    Google Scholar 

  31. Van Meir EG, Hadjpanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for a malignant glioma. CA Cancer J Clin. 2010;60(3):166–93.

    Article  PubMed  Google Scholar 

  32. Norden AD, Drappatz J, Wen PY. Antiangiogenic therapies for high-grade glioma. Nat Rev Neurol. 2009;5(11):610–20.

    Article  PubMed  CAS  Google Scholar 

  33. Prados M, Cloughesy T, Samant M, et al. Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab. Neurooncology. 2011;13(1):143–51.

    CAS  Google Scholar 

  34. Chamberlain MC. Bevacizumab for the treatment of recurrent glioblastoma. Clin Med Insights Oncol. 2011;5:117–29.

    Article  PubMed  CAS  Google Scholar 

  35. Epenetos AA, Munro AJ, Stewart S, et al. Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabelled monoclonal antibodies. J Clin Oncol. 1987;5(12):1890–9.

    PubMed  CAS  Google Scholar 

  36. Larson SM. Radiolabelled monoclonal anti-tumor antibodies in diagnosis and therapy. J Nucl Med. 1985;26(5):538–45.

    PubMed  CAS  Google Scholar 

  37. Buraggi GL, Callegaro L, Mariani G, et al. Imaging with 131I-labeled monoclonal antibodies to a high-molecular-weight melanoma-associated antigen in patients with melanoma: efficacy of whole immunoglobulin and its F(ab’)2 fragments. Cancer Res. 1985;45(7):3378–87.

    PubMed  CAS  Google Scholar 

  38. Kim JA, Triozzi PL, Martin Jr EW. Radioimmuguided surgery for colorectal cancer. Oncology. 1993;7(2): 55–64.

    PubMed  Google Scholar 

  39. Fazio F, Paganelli G. Antibody-guided scintigraphy: targeting of the “magic bullet”. Eur J Nucl Med. 1993;20(12):1138–40.

    Article  PubMed  CAS  Google Scholar 

  40. Hazra DK, Britton KE, Lahiri VL, Gupta AK, Khanna P, Saran S. Immunotechnological trends in radioimmunotargeting: from ‘magic bullet’ to ‘smart bomb’. Nucl Med Commun. 1995;16(2):66–75.

    Article  PubMed  CAS  Google Scholar 

  41. Wessels BW, Rogus RD. Radionuclide selection and model absorbed dose calculations for radiolabeled tumor associated antibodies. Med Phys. 1984;11(5): 638–45.

    Article  PubMed  CAS  Google Scholar 

  42. Chinol M, Hnatowich DJ. Generator-produced yttrium-90 for radioimmunotherapy. J Nucl Med. 1987;28(9):1465–70.

    PubMed  CAS  Google Scholar 

  43. Goldenberg DM, Griffiths GL. Radioimmunotherapy of cancer: arming the missiles. J Nucl Med. 1992;33(6): 1110–2.

    PubMed  CAS  Google Scholar 

  44. Chetanneau A, Barbet J, Peltier P, et al. Pretargetted imaging of colorectal cancer recurrences using an In-111-labelled bivalent hapten and a biospecific antibody conjugate. Nucl Med Commun. 1994;15(12): 972–80.

    Article  PubMed  CAS  Google Scholar 

  45. Magnani P, Paganelli G, Modorati G, et al. Quantitative comparison of direct antibody labeling and tumor ­pretargeting in uveal melanoma. J Nucl Med. 1996;37(6): 967–71.

    PubMed  CAS  Google Scholar 

  46. Wilchek M, Bayer EA. The avidin biotin complex in bioanalytical applications. Anal Biochem. 1988; 171(1):1–32.

    Article  PubMed  CAS  Google Scholar 

  47. Paganelli G, Magnani P, Zito F, et al. Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients. Cancer Res. 1991;51(21):5960–6.

    PubMed  CAS  Google Scholar 

  48. Paganelli G, Chinol M, Grana C, et al. Optimization of the three-step pretargeting approach for diagnosis and therapy in cancer patients. J Nucl Med. 1995; 36(abs):225P.

    Google Scholar 

  49. Paganelli G, Grana C, Chinol M, et al. Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin. Eur J Nucl Med. 1999;26(4): 348–57.

    Article  PubMed  CAS  Google Scholar 

  50. Zagzag D, Friedlander DR, Dosik J, et al. Tenascin-C expression by angiogenic vessels in human astrocytomas and by human brain endothelial cells in vitro. Cancer Res. 1996;56(1):182–9.

    PubMed  CAS  Google Scholar 

  51. Leins A, Riva P, Lindstedt R, Davidoff MS, Mehraein P, Weis S. Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma. Cancer. 2003;98(11):2430–9.

    Article  PubMed  CAS  Google Scholar 

  52. Wilkstrand CJ, Zalutsky MR, Bigner DD. Therapy of brain tumors with radiolabeled antibodies. In: Liau LM, Becker DP, Cloughsey TF, Bigner DD, editors. Brain tumor immunotherapy. Totwa: Humana Press; 2001. p. 205–29.

    Google Scholar 

  53. Herold-Mende C, Mueller MM, Bonsanto MM, Schmitt HP, Kunze S, Steiner HH. Clinical impact and functional aspects of tenascina-C expression during glioma progression. Int J Cancer. 2002;98(3): 362–9.

    Article  PubMed  CAS  Google Scholar 

  54. Grana C, Chinol M, Robertson C, et al. Pretargeted adjuvant radioimmunotherapy with yttrium-90-biotin in malignant glioma patients: a pilot study. Br J Cancer. 2002;86(2):207–12.

    Article  PubMed  CAS  Google Scholar 

  55. Grana CM, Chinol M, De Cicco C, et al. Eleven-year experience with the Avidin-Biotin pretargeting system in glioblastoma: toxicity, efficacy and survival. The Open Nuclear Medicine Journal. 2012;4:14–20.

    Article  PubMed  Google Scholar 

  56. Liu BL, Cheng JX, Zhang X, Zhang W. Controversies concerning the application of brachitherapy in central nervous system tumours. J Cancer Res Clin Oncol. 2010;136(2):173–85.

    Article  PubMed  Google Scholar 

  57. Riva P, Franceschi G, Frattarelli M, et al. Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with 90Y: a phase I study. Clin Cancer Res. 1999;5 Suppl 10:3275s–80.

    PubMed  CAS  Google Scholar 

  58. Cokgor I, Akabani G, Kuan CT, et al. Phase I trial results of iodine-131–labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas. J Clin Oncol. 2000; 18(22):3862–72.

    PubMed  CAS  Google Scholar 

  59. Riva P, Franceschi G, Riva N, Casi M, Santimaria M, Adamo M. Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach. Eur J Nucl Med. 2000;27(5):601–9.

    Article  PubMed  CAS  Google Scholar 

  60. Goetz C, Riva P, Poepperl G, et al. Locoregional radioimmunotherapy in selected patients with malignant gliomas: experiences, side effects and survival times. J Neurooncol. 2003;62(3):321–8.

    Article  PubMed  CAS  Google Scholar 

  61. Reardon DA, Rich JN, Friedman HS, Bigner DD. Recent advances in the treatment of malignant astrocytoma. J Clin Oncol. 2006;24(8):1253–65 (review).

    Google Scholar 

  62. Zalutsky MR. Current status of therapy of solid tumors: brain tumour therapy. J Nucl Med. 2005; 46(Suppl 1):151S–6S (review).

    Google Scholar 

  63. Zalutsky MR, Reardon DA, Akabani G, et al. Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6. J Nucl Med. 2008;49(1):30–8.

    Article  PubMed  CAS  Google Scholar 

  64. Paganelli G, Bartolomei M, Ferrari M, et al. Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients: phase I study and preliminary therapeutic results. Cancer Biother Radiopharm. 2001;16(3): 227–35.

    Article  PubMed  CAS  Google Scholar 

  65. Bartolomei M, Mazzetta C, Handkiewicz-Junak D, et al. Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and temozolomide. Q J Nucl Med Mol Imaging. 2004;48(3):220–8.

    PubMed  CAS  Google Scholar 

  66. Boiardi A, Bartolomei M, Silvani A, et al. Intratumoral delivery of mitoxantrone in association with 90-Y radioimmunotherapy (RIT) in recurrent glioblastoma. J Neurooncol. 2005;72(2):125–31.

    Article  PubMed  CAS  Google Scholar 

  67. Cremonesi M, Ferrari M, Chinol M, et al. Three-step radioimmunotherapy with yttrium-90 biotin: dosimetry and pharmacokinetics in cancer patients. Eur J Nucl Med. 1999;26(2):110–20.

    Article  PubMed  CAS  Google Scholar 

  68. Bartolomei M, Bodei L, De Cicco C, et al. Peptide receptor radionuclide therapy with (90)Y-DOTATOC in recurrent meningioma. Eur J Nucl Med Mol Imaging. 2009;36(9):1407–16.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Mrs. Deborah Console for editing the manuscript.

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Authors and Affiliations

  1. Division of Nuclear Medicine, European Institute of Oncology, Via Ripamonti, 435-20141, Milan, Italy

    Chiara Maria Grana & Giovanni Paganelli

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  1. Chiara Maria Grana
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  2. Giovanni Paganelli
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Correspondence to Giovanni Paganelli .

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Editors and Affiliations

  1. Tirocenter Nuclear Medicine Center, Adnan Saygun Cad. 3, Istanbul, 34340, Turkey

    Cumali Aktolun

  2. & Molecular Imaging, New York-Presbyterian Hospital, Division of Nuclear Medicine, East 68th Street 525, New York, 10065, New York, USA

    Stanley J. Goldsmith

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Grana, C.M., Paganelli, G. (2013). Radioimmunotherapy in Brain Tumors. In: Aktolun, C., Goldsmith, S. (eds) Nuclear Medicine Therapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4021-5_7

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