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Boron Neutron Capture Therapy of Glioblastoma Multiforme Using the p-Boronophenylalanine-Fructose Complex and Epithermal Neutrons

  • J. A. Coderre
  • R. Bergland
  • M. Chadha
  • A. D. Chanana
  • E. Elowitz
  • D. D. Joel
  • H. B. Liu
  • D. N. Slatkin
  • L. Wielopolski

Abstract

The amino acid analog p-boronophenylalanine (BPA) has been under investigation at Brookhaven National Laboratory (BNL) as a neutron capture agent for BNCT of glioblastoma multiforme (GBM) for the past six years. BPA, delivered orally, is effective in BNCT of the intracerebral 9L rat gliosarcoma1. Histologic examination of the brains of long-term BNCT survivors showed scar tissue replacing the tumor with no serious damage to the contiguous normal brain2. A series of 17 patients undergoing surgical removal of tumor (GBM or melanoma) received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT3. BPA can be solubilized at neutral pH by complexation with fructose4. BPA-fructose (BPA-F) is administered intravenously (iv) for thermal neutron-based BNCT of melanoma in Japans. Intraperitoneal (ip) injection of the soluble BPA-F complex produces much higher tumor boron concentrations in the rat intracerebral 9L gliosarcoma than were previously possible using oral administration of BPA. Higher boron concentrations have allowed higher radiation doses to be delivered to the tumor while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. This resulted in long-term survival of over 90% of BNCT-treated rats6. Surviving rats show no obvious neurologic deficit. We have measured the relative biological effectiveness (RBE) of the various high-linear energy transfer (LET) components of the total BNCT dose in both tumor and normal tissues. Our data indicate a therapeutic ratio (tumor dose/normal tissue dose) in excess of 5:1 (Coderre et al., these proceedings). A biodistribution study of iv BPA-F in patients with high-grade gliomas is reported elsewhere in these proceedings (Bergland et al.,these proceedings).

Keywords

Glioblastoma Multiforme Boron Concentration Biodistribution Study Boron Neutron Capture Therapy Relative Biological Effective 
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 Science+Business Media New York 1996

Authors and Affiliations

  • J. A. Coderre
    • 1
  • R. Bergland
    • 2
  • M. Chadha
    • 3
  • A. D. Chanana
    • 1
  • E. Elowitz
    • 2
  • D. D. Joel
    • 1
  • H. B. Liu
    • 1
  • D. N. Slatkin
    • 1
  • L. Wielopolski
    • 1
  1. 1.Medical DepartmentBrookhaven National LaboratoryUptonUSA
  2. 2.Department of NeurosurgeryBeth Israel Medical CenterNew YorkUSA
  3. 3.Department of Radiation OncologyBeth Israel Medical CenterNew YorkUSA

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