The New Generation of Particle Therapy Focused on Boron Element (Boron Neutron Capture Therapy; BNCT) - The World's First Approved BNCT Drug

Boron neutron capture therapy (BNCT) is a type of radiation therapy and a new modality for cancer treatment. The radiation used in BNCT is a very low energy neutron called a "thermal neutron", and unlike other radiation, it has no effect on treating cancer on its own. However, when this neutron collides with boron-10 (B-10), which is a stable isotope of boron, fission occurs into a high-energy helium nucleus (alpha-particle) and a lithium nucleus. Moreover, the effect of this fission reaction is limited to a range of about 10 mu m, which corresponds to the approximate size of one cell. Therefore, the basic principle of BNCT is "cell-selective" radiation therapy that only damages cells that have taken up B-10 present in the area irradiated with thermal neutrons. For the practical application of BNCT, it is indispensable to generate a boron drug capable of selectively accumulating B-10 in cancer cells. We have successfully developed a boron drug for BNCT targeting amino acid transporters. We have obtained manufacturing and marketing approval for the world's first boron drug for BNCT, Steboronine (R) intravenous drip bag 9000 mg/300 mL (March 25, 2020), for indications of locally unresectable recurrent or advanced unresectable head and neck cancer. This uses Borofalan (B-10), which is B-10 introduced into L-phenylalanine, as a drug substance. This review describes the progress of drug development and future prospects of boron drugs for BNCT.