ET-5 Biological effects of simultaneous use of multiple drugs in neutron capture therapy using rat brain tumor model

Abstract

The world’s first clinical trial of boron neutron capture therapy (BNCT), which treats malignant brain tumors with a single dose of neutron irradiation using multiple boron drugs simultaneously, was performed at our institution, and its excellent results have stimulated BNCT research around the world. BNCT is a particle irradiation therapy that biologically targets cancer cells, and is expected to be a “new option for cancer treatment” because it can deliver a dose of radiation at the cellular level. In the case of BNCT using a combination of multiple drugs, a method to appropriately consider the biological effects of the combination in the dose calculation has not been established. At present, BNCT based on an accelerator-based irradiation system and a boron drug (BPA) based on essential amino acids has been approved by the regulatory approval for head and neck cancer and has shown good results in brain tumors. As basic research, we have continued to develop new boron drugs, which will be essential in the future, and have explored the interpretation of the biological effects of multiple boron drugs in combination and the optimal conditions required for drug development. The survival curve of BNCT in a rat brain tumor model showed that the effect of the new drug alone was comparable to that of BPA, and the effect of the combination was improved, but the effect of the combination did not match the prediction of the combined biological effect derived from each drug. However, it has been found that the effect of the combination does not match the prediction based on the combination of biological effects derived from each drug. In other words, even if the equivalent X-ray equivalent dose (Gy-Eq) is calculated, the combined effect of some drugs exceeds the prediction, while the combined effect of other drugs is poor.