Tolerance of normal human brain to boron neutron capture therapy

Coderre, Jeffrey A.; Hopewell, J. W.; Turcotte, J; Riley, Kent J.; Binns, Peter J.; Kiger, W. S.; Harling, O. K.

doi:10.1016/j.apradiso.2004.05.009

Cited by 29 publications

(15 citation statements)

References 13 publications

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“…None of the patients had a lifethreatening adverse event or died within 30 days from the date of BNCT, suggesting that BNCT administered after conventional brain tumor irradiation is feasible with these dosages. The mean average weighted normal brain dose remained low (3 Gy [W]), which may explain the relatively good tolerability of BNCT in the present study (21). 12 (7,15) 38 (16,59) * The weighting factor applied for the nitrogen and hydrogen dose was 3.2, assuming 1.84 w-% nitrogen and 10.57 w-% hydrogen composition for the brain.…”

Section: Discussionmentioning

confidence: 93%

l-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

Kankaanranta

Seppälä

Koivunoro

et al. 2011

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussionmentioning

confidence: 93%

l-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

Kankaanranta

Seppälä

Koivunoro

et al. 2011

International Journal of Radiation Oncology*Biology*Physics

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“…Longer infusions of BPA, carried out in Sweden (63), may marginally have increased the median survival time, but the dose escalation studies with BPA have reached the point where normal brain tolerance has become the limiting factor. The occurrence of the somnolence syndrome in patients treated with the higher radiation doses has been reported (64), which indicates that dose escalation trials with BPA as the single boron delivery agent, have reached a limit both in terms of the doses of BPA and neutrons. With BPA, there was a significant amount of boron in normal brain, and this undoubtedly contributed to the brain dose and the occurrence of the somnolence syndrome.…”

Section: Discussionmentioning

confidence: 99%

Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4

Yang¹,

Barth²,

Wu³

et al. 2006

Clinical Cancer Research

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Purpose: The purpose of the present study was to evaluate a boronated EGFRvIII-specific monoclonal antibody, L8A4, for boron neutron capture therapy (BNCT) of the receptor-positive rat glioma, F98 npEGFRvIII . Experimental Design: A heavily boronated polyamido amine (PAMAM) dendrimer (BD) was chemically linked to L8A4 by two heterobifunctional reagents, N-succinimidyl 3-(2-pyridyldithio)propionate and N-(k-maleimidoundecanoic acid)hydrazide. For in vivo studies, F98 wild-type receptor-negative or EGFRvIII human gene-transfected receptor-positive F98 npEGFRvIII glioma cells were implanted i.c. into the brains of Fischer rats. Biodistribution studies were initiated 14 days later. Animals received [125 I]BD-L8A4 by either convection enhanced delivery (CED) or direct i.t. injection and were euthanized 6, 12, 24, or 48 hours later. Results: At 6 hours, equivalent amounts of the bioconjugate were detected in receptor-positive and receptor-negative tumors, but by 24 hours the amounts retained by receptor-positive gliomas were 60.1% following CED and 43.7% following i.t. injection compared with 14.6% ID/g by receptor-negative tumors. Boron concentrations in normal brain, blood, liver, kidneys, and spleen all were at nondetectable levels (<0.5 Ag/g) at the corresponding times. Based on these favorable biodistribution data, BNCT studies were initiated at the Massachusetts Institute of Technology Research Reactor-II. Rats received BD-L8A4 (f40 Ag

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“…pressure, resulting from tumor necrosis and the associated cerebral edema (141,163,165). The most frequently observed neurologic side effect associated with the higher radiation doses, other than the residual tumor volume -related effects, was radiation-related somnolence (168). This is a wellrecognized effect following whole-brain photon irradiation (169), especially in children with leukemia or lymphoma, who have received central nervous system irradiation.…”

Section: Clinical Studies Of Boron Neutron Capture Therapy For Braintmentioning

confidence: 99%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

912

666

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Background: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer A particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. Boron Delivery Agents: Two boron drugs have been used clinically, sodium borocaptate (Na 2 B 12 H 11 SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations (f20 Ag/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boroncontaining amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. Clinical Trials: Current or recently completed clinical trials have been carried out inJapan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of ''debulking'' surgery to remove as much of the tumor as possible, followed by BNCTat varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. Conclusions: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCTcould move forward as a treatment modality.

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Tolerance of normal human brain to boron neutron capture therapy

Cited by 29 publications

References 13 publications

l-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

l-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

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