title: Synthesis and evaluation of a boronated nitroimidazole for boron neutron capture therapy.
abstract: We postulated that nitroimidazoles, previously used for radiosensitizing solid tumors, may be interesting templates as carriers of 10B for boron neutron capture therapy. To test this hypothesis, we synthesized a 10B-enriched nitroimidazole, 1-2[(undecahydro-closo-dodecaborato)thio]ethyl]-2- methyl-5-nitroimidazole (imidocaptate), by coupling the Cs salt of BSH (Cs2-10B12H11SH) with 1-(2-bromoethyl)-2-methyl-5-nitroimidazole followed by purification of the adduct. Imidocaptate was taken up by V-79 cells in culture and showed no inherent toxicity under euoxic conditions up to 1.05 mM (126 micrograms of 10B/mL of culture medium). Imidocaptate showed a dose-dependent decrease in D0 when the treated cells were irradiated with a thermal neutron beam. At the highest dose tested (126 micrograms of 10B/mL of culture medium), the ratio of control to sample D0 values was 2.6 for both linear quadratic and single-hit multitarget models. At 33 micrograms of 10B/mL, imidocaptate showed a control/treated D0 ration (1.5) equal to that observed with the disulfide form of BSH at 28 micrograms of 10B/mL. Compared to BSH and its disulfide, the reduced toxicity and equipotency of imidocaptate suggest that this agent may be useful for boron neutron capture therapy of cancer.
authors.affiliation: Department of Veterinary Physiology, Pharmacology and Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Swenson
authors.forename: B H
authors.initials: BH
authors.lastname: Laster
authors.forename: R L
authors.initials: RL
authors.lastname: Metzger
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009369:Neoplasms / Q000532:radiotherapy; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001896:Boron Compounds; D009593:Nitroimidazoles; C100472:imidocaptate