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Radioimmunotherapy of Neuroblastoma

  • Shakeel Modak
  • Kim Kramer
  • Neeta Pandit-Taskar
Chapter
Part of the Medical Radiology book series (MEDRAD)

Abstract

Effecting cures in patients with neuroblastoma remains a major challenge despite aggressive multimodality therapy. Antibody-mediated anti-GD2 immunotherapy has recently been shown to improve survival and is now considered part of frontline therapy for high-risk neuroblastoma. Radioimmunotherapy has the potential to target effective radiation to neuroblastoma, at the same time avoiding the toxicities of external beam radiotherapy which are often severe in children. The anti-GD2 radiolabeled antibodies 131I-3F8 and 131I-14G2a have been shown to target neuroblastoma and have been used for radioimmunodetection and are more specific and sensitive at detecting disease than 131I-MIBG. Toxicities, biodistribution and dosimetry for intravenous 131I-3F8 have been determined in phase I and II trials in patients with neuroblastoma. Myelosuppression, reversible with hematopoietic stem cell rescue is a major toxicity. Patients also experienced pain and allergic reactions. 131I-3F8 has been injected into the ventricles via Ommaya injection in leptomeningeal neuroblastoma without long-term toxicities being observed. Intra-Ommaya anti-4Ig-B7H3 radiolabeled monoclonal antibody 131I-8H9 is also being studied in a phase I study for patients with leptomeningeal disease. Radioimmunotherapy with both radioiodinated antibodies is a key component of a therapeutic regimen for relapsed leptomeningeal neuroblastoma which has resulted in encouraging long-term survival rates in a majority of patients with this hitherto uniformly lethal disease. Detailed dosimetry information and high-quality images have been acquired via PET imaging after intra-Ommaya injections of the radioimmunoconjugates 124I-3F8 and 124I-8H9. The recent availability of humanized versions of 3F8 and 8H9 may permit the clinical study of newer and potentially more effective radioimmunoconjugates for the radioimmunotherapy of neuroblastoma. However, for the expanded clinical investigation of radioimmunotherapy and its inclusion in the armamentarium of therapies for neuroblastoma and other “orphan” pediatric malignancies, major policy changes in drug development strategies are necessary.

Keywords

Minimal Residual Disease Central Nervous System Relapse Desmoplastic Small Round Cell Tumor Pediatric Solid Tumor Autologous Stem Cell Rescue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Shakeel Modak
    • 1
  • Kim Kramer
    • 1
  • Neeta Pandit-Taskar
    • 2
  1. 1.Departments of PediatricsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Departments of RadiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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