The usefulness of 2-nitroimidazole-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy

We evaluated the usefulness of five new 10B-compounds (TX-2016, TX-2017, TX-2018, TX-2041, and TX-2042) as 10B-carriers in boron neutron capture therapy (BNCT). They are 2-nitroimidazole-sodium borocaptate-10B (BSH) conjugates, that is, hybrid compounds that have both hypoxic tumor cell sensitizing unit under γ-ray irradiation, 2-nitroimidazoles, and thermal neutron-sensitizing unit, BSH. 10B distribution analyses in tumors and blood indicated that TX-2041 has the most favorable characteristics for localizing a sufficient amount of 10B into tumors and keeping the 10B concentration high during neutron beam irradiation. In addition, TX-2041 showed a significantly higher radio-sensitization effect with reactor thermal neutron beams than BSH on both total (=proliferating (P) + quiescent (Q)) and hypoxia-rich Q cell populations in solid tumors. Further, TX-2041 clearly demonstrated a radio-sensitization effect with γ-rays on both cell populations, which could never be achieved by BSH. 10B-carriers with a hypoxic tumor cell-sensitizing effect on tumors with γ-rays as well as the potential to selectively localize and keep 10B in tumors, such as TX-2041, are promising for use in actual BNCT.