Boron Neutron Capture Therapy

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KIRIHATA, Mitsunori, Ph.D.Professor Lab. of Medicinal Chemistry for Boron DrugResearch Center for BNCTOsaka Prefecture UniversityBoron agentsDeveloping high-performance boron agents to selectively concentrate boron in tumor cellsBoron is a chemical element with atomic number 5 in group 13 and period 2 of the periodic chart. Although it is common in the form of boric acid in rock, groundwater, surface water, and plants, it is not present in the human body. Natural boron exists in two isotopes with mass numbers of 10 (10B) and 11 (11B) in a proportion of about 1:4, and only 10B is capable of absorbing (capturing) neutrons. Consequently, high-purity 10B (enriched 10B) is necessary as a raw material in order to manufacture the boron agents that are used in BNCT. Currently, only a small number of countries, including Japan and the U.S., have plants capable of manufacturing enriched 10B by sorting 10B and 11B in natural boron compounds and supplying it in large quantities. Pharmaceutical-grade boron compounds are manufactured using this enriched 10B in Japan, the Czech Republic, and other countries. Properties required of 10B compounds and boron agentsL-BPA (L-p-boronophenylalanine [paraboronophenylalanine])1L-BPA was initially used in BNCT for melanoma due to its similarity to L-phenylalanine, which is the substance from which melanin biosynthesis begins. Later, researchers realized that it has an exceptionally high propensity to accumulate in other tumors as well, and today it is used in BNCT for brain tumors and head and neck cancer. Additionally, because its high degree of hydrophobicity means that it almost never dissolves in water under neutral conditions, it is combined with a water-soluble substance such as D-fructose to form a water-soluble complex that is then used as a boron agent.NH2HOOHCO2H10BL-BPA210B manufacturing plant (courtesy of Stella Chemifa Corporation)Boron-10 and the manufacture of high-purity, enriched boron-10they must not have any pharmaceutical effects themselves and must function only as a boron delivery molecule (in this property, they differ substantially from normal drugs),they must not be metabolized but must instead remain in tumor tissue for a certain period of time, they must exhibit low toxicity since they are administered directly into the blood.Boron compounds for use in BNCT must exhibit the following principal properties:Additionally, research to date has pointed to the impor-tance of properties such as the balance of hydrophobic and hydrophilic tendencies and the proportion of each mole-cule’s chemical makeup accounted for by the element boron. Currently, two boron compounds are being used in clinical research into BNCT: BPA, which has the structure of an amino acid, and BSH, which has a cluster-like structure.they must accumulate selectively (the ratio of the concentration in tumor cells to the concentration in normal cells [T/N] must be greater than or equal to 3) and in large volumes (at a 10B concentration of 20 to 40 ppm), High-purity boron compounds for use in BNCT9

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