Boron Neutron Capture

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Fused Polyhedron Borane Dianion Inventor(s): Narayan Hosmane, Robert Spielvogel Abstract Boron Neutron Capture Therapy (BNCT) is a potentially powerful form of radiotherapy involving the preferential incorporation of 10B containing compounds into tumor cells, followed by irradiation of the tumor by thermal neutrons. On absorption of a neutron, the B atom undergoes a fission reaction to produce high linear energy transfer (LET) He and Li particles that are confined to a radius comparable to the dimension of a cell. Thus, irradiation will result in the destruction of the tumor cell in which the particles are generated, with little damage to the surrounding tissue. Several requirements must be met in order for this therapy to be effective. (i) A concentration of 25-30 µg B atoms/g of tumor must be achieved; (ii) a tumor: normal tissue (T: N) ratio of the boron delivery agent greater than 1 is necessary; and (iii) the boron drug should be of low toxicity. Among many boron compounds synthesized, the carborane containing amino acids, carbohydrates, nucleic acid bases, nucleosides and nucleotides are considered to be most useful for the preparation of boron drugs. A large number of nucleosides, attached with various boron moieties at different positions of either the base or the sugar, have been synthesized and evaluated biologically for use in BNCT. Nonetheless, all of the previous nucleotide carborane constructs have been joined by hydrolytically sensitive linkages. The rationale for the design and synthesis of boron containing nucleosides is that such compounds may concentrate selectively in rapidly dividing tumor cells, and following their conversion to the corresponding nucleotides, may be trapped within the cell or, ideally, incorporated into nuclear DNA of tumor cells. In the case of BNCT, such a nuclear localization of boron carrier, i.e., boronated nucleoside, would be advantageous since the effect of neutron capture reaction in nucleus is 2-5 times greater than in cytoplasm. Nevertheless, the ideal drug for BNCT should exhibit stability under physiological conditions and the construction of a species involving direct P-C(cage)-nucleotide linkages is therefore warranted. Potential commercial use and users: The incorporation of this compound in the drug would provide double the concentration of boron that is needed for the Boron Neutron Capture Therapy (BNCT) in the treatment of cancer. Advantages: The destruction of the cell is limited to only the cancer cells that preferentially intake the boron drug since the BNC takes place within the cell. The radiation due to alpha particles, produced in the BNCT, has a path length of 8-10 microns, that is the size of a cell. Status: Patent No. 6,525,224