Advertisement

European Journal of Nuclear Medicine

, Volume 26, Issue 4, pp 348–357 | Cite as

Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin

  • Giovanni Paganelli
  • Chiara Grana
  • Marco Chinol
  • Marta Cremonesi
  • Concetta De Cicco
  • Filippo De Braud
  • Chris Robertson
  • Stefano Zurrida
  • Chiara Casadio
  • Stefania Zoboli
  • Antonio G. Siccardi
  • Umberto Veronesi
Original article

Abstract.

While the incidence of brain tumours seems to be increasing, median survival in patients with glioblastoma remains less than 1 year, despite improved diagnostic imaging and neurosurgical techniques, and innovations in treatment. We have developed an avidin-biotin pre-targeting approach for delivering therapeutic radionuclides to gliomas, using anti-tenascin monoclonal antibodies, which seems potentially effective for treating these tumours. We treated 48 eligible patients with histologically confirmed grade III or IV glioma and documented residual disease or recurrence after conventional treatment. Three-step radionuclide therapy was performed by intravenous administration of 35 mg/m2 of biotinylated anti-tenascin monoclonal antibody (1st step), followed 36 h later by 30 mg of avidin and 50 mg of streptavidin (2nd step), and 18–24 h later by 1–2 mg of yttrium-90-labelled biotin (3rd step). 90Y doses of 2.22–2.96 GBq/m2 were administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m2. Tumour mass reduction (>25%–100%), documented by computed tomography or magnetic resonance imaging, occurred in 12/48 patients (25%), with 8/48 having a duration of response of at least 12 months. At present, 12 patients are still in remission, comprising four with a complete response, two with a parital response, two with a minor response and four with stable disease. Median survival from 90Y treatment is 11 months for grade IV glioblastoma and 19 months for grade III anaplastic gliomas. Avidin-biotin based three-step radionuclide therapy is well tolerated at the dose of 2.2 GBq/m2, allowing the injection of 90Y-biotin without bone marrow transplantation. This new approach interferes with the progression of high-grade glioma and may produce tumour regression in patients no longer responsive to other therapies.

Key words: Biotinylated monoclonal antibodies Tumour pre-targeting Avidin/biotin glioma radio-immunotherapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Giovanni Paganelli
    • 1
  • Chiara Grana
    • 1
  • Marco Chinol
    • 1
  • Marta Cremonesi
    • 1
  • Concetta De Cicco
    • 1
  • Filippo De Braud
    • 2
  • Chris Robertson
    • 3
  • Stefano Zurrida
    • 5
  • Chiara Casadio
    • 4
  • Stefania Zoboli
    • 1
  • Antonio G. Siccardi
    • 6
  • Umberto Veronesi
    • 5
  1. 1.Division of Nuclear Medicine, European Institute of Oncology, Milan, ItalyIT
  2. 2.Division of Medical Oncology, European Institute of Oncology, Milan, ItalyIT
  3. 3.Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, ItalyIT
  4. 4.Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, ItalyIT
  5. 5.Scientific Director Office, European Institute of Oncology, Milan, ItalyIT
  6. 6.San Raffaele Scientific Institute and University of Milan, ItalyIT

Personalised recommendations