The usefulness of 2-nitroimidazole-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy.
We evaluated the usefulness of five new (10)B-compounds (TX-2016, TX-2017, TX-2018, TX-2041, and TX-2042) as (10)B-carriers in boron neutron capture therapy (BNCT). They are 2-nitroimidazole-sodium borocaptate-(10)B (BSH) conjugates, that is, hybrid compounds that have both hypoxic tumor cell sensitizing unit under gamma-ray irradiation, 2-nitroimidazoles, and thermal neutron-sensitizing unit, BSH. (10)B distribution analyses in tumors and blood indicated that TX-2041 has the most favorable characteristics for localizing a sufficient amount of (10)B into tumors and keeping the (10)B 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 gamma-rays on both cell populations, which could never be achieved by BSH. (10)B-carriers with a hypoxic tumor cell-sensitizing effect on tumors with gamma-rays as well as the potential to selectively localize and keep (10)B in tumors, such as TX-2041, are promising for use in actual BNCT.
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan. smasuna@rri.kyoto-u.ac.jp
S
S
Masunaga
H
H
Nagasawa
M
M
Hiraoka
Y
Y
Sakurai
Y
Y
Uto
H
H
Hori
K
K
Nagata
M
M
Suzuki
A
A
Maruhashi
Y
Y
Kinashi
K
K
Ono
D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy*; D015687:Cell Hypoxia; D002470:Cell Survival / Q000528:radiation effects; D004337:Drug Carriers; D005260:Female; D007554:Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D008809:Mice, Inbred C3H
D001896:Boron Compounds; D004337:Drug Carriers; D007554:Isotopes