Boron Neutron Capture Therapy

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Yutaka Mishima, a professor of dermatology at Kobe Univer-sity, conducted many years of research in an effort to treat malignant melanoma (skin cancer) exhibiting X-ray resis-tance with BNCT. He focused on L-paraBoronophenylalanine (L-BPA, referred to as “BPA” below) as an analog of tyrosine, which is a precursor of melanin, and conducted basic research to apply BPA in BNCT as melanoma-specific boron compound. As a result, there was a large difference in BPA concentration between malignant melanoma cells and normal cells. Through subsequent research using FBPA PET imag-ing, it was discovered that the compound accumulated not only in malignant melanoma, but also in various malignant tumors. It is thought that this fact is accounted for by the increased level of amino acid transport in malignant tumor cells, and today the effects of BPA-BNCT on numerous types of tumors are being studied. BPA was first used clinically in BNCT to treat a malignant melanoma in 1987 by Mishima and his team. The compound was first used in BNCT to treat a patient with recurrent malignant glioma in February 1994 using the KUR. This trial preceded a similar study at Brookha-ven National Laboratory in the U.S. by about seven months.BPA differs significantly from BSH in that it is selectively absorbed by cancer cells, and it is fair to say that BNCT could first be called a technique for selective cancer cell treatment with the advent of BPA.At the end of the 1950s, irradiation experiments using small animals as basic research began at the Japan Research Reactor No.1 (JRR-1) and the Hitachi Training Reactor (HTR). In 1968, a team led by Hiroshi Hatanaka began administering BNCT to patients with malignant brain tumors using a new boron compound (Na2B12H11SH, commonly known as BSH). The HTR and the Musashi Institute of Tech-nology Reactor (MuITR), which was modified for medical use, were used as neutron sources, and a high-purity thermal neutron irradiation field developed at the heavy-water facility of the Kyoto University Research Reactor (KUR) was also used in 1974. Since the ability of the neutron beam (consist-ing of thermal neutrons) to penetrate deep tissue was limited, irradiation was performed during a craniotomy (in a process known as intraoperative irradiation). The compound BSH, of which each molecule has 12 10B atoms, is easy to use since it excels in its ability to transport 10B and offers high water solubility. Whereas BSH is prevented from penetrating brain tissue by the blood-brain barrier in normal brains, the failure of this barrier function allows it to penetrate, and accumulate in, malignant brain tumors, resulting in a large concentration difference. However, the compound’s properties are not such that cancer cells actively accumulate it. Although the results obtained by Hatanaka were favorable and suggested the efficacy of BNCT, he was unable to convince neurosurgeons and radiation oncologists of the usefulness of this treatment.BSH : The first clinically effective boron compoundBPA: A boron compound that accelerated new developments in BNCTOno, Koji, M.D., Ph.D. Emeritus and Visiting ProfessorParticle Radiation Oncology Research CenterResearch Reactor InstituteKyoto University2

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