Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer

Abstract

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, the United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials. Finally, we will summarize the critical issues that must be addressed if BNCT is to become a more widely established clinical modality for the treatment of those malignancies for which there currently are no good treatment options.

Treatment of high-grade glioma in children

“…Boron nötron kapma tedavisi (Boron neutron capture therapy), biyokimyasal bir hedef RT alanı sağlayarak yüksek miktardaki radyasyonu etraf dokuya çokazını yansıtarak verebilen bir yöntemdir. [50] Sonuç olarak, YDG ve BSG'de prognoz kötü, supratentorial tümörlerde tam/tama yakın rezeksiyon en önemli prognotik faktödür. YDG ve BSG'de RT'nin çok önemli bir yeri vardır.…”

Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C

“…Due to the short path of the emitted particles, a lethal damage is produced on tumor cells, preserving surrounding normal tissue. 1 The precise knowledge about the location of boron compounds in tumor and surrounding tissue is essential in order to optimize the treatment protocol. The variety of tissue structures will accumulate different amounts of boron and this will affect dose distribution.…”

Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy

“…1,2 For this therapy to be successful, boron-10 must be accumulated in concentrations of more than 10-20 ppm in the target tissue. 3,4 For the therapy to be successful, the chemical form of the boron compounds, and their possible binding to components of the blood and tissues, are of little importance as long as there is a sufficient amount of boron in the target tissue. As the amount of boron in the tumor should be as high as possible, compounds should contain boron units with as many boron atoms as possible.…”