title: Biodistribution of sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) in an oral cancer model.
abstract: Boron neutron capture therapy (BNCT) is based on selective accumulation of ¹⁰B carriers in tumor followed by neutron irradiation. We previously proved the therapeutic success of BNCT mediated by the boron compounds boronophenylalanine and sodium decahydrodecaborate (GB-10) in the hamster cheek pouch oral cancer model. Based on the clinical relevance of the boron carrier sodium borocaptate (BSH) and the knowledge that the most effective way to optimize BNCT is to improve tumor boron targeting, the specific aim of this study was to perform biodistribution studies of BSH in the hamster cheek pouch oral cancer model and evaluate the feasibility of BNCT mediated by BSH at nuclear reactor RA-3. The general aim of these studies is to contribute to the knowledge of BNCT radiobiology and optimize BNCT for head and neck cancer. Sodium borocaptate (50 mg ¹⁰B/kg) was administered to tumor-bearing hamsters. Groups of 3-5 animals were killed humanely at nine time-points, 3-12 h post-administration. Samples of blood, tumor, precancerous pouch tissue, normal pouch tissue and other clinically relevant normal tissues were processed for boron measurement by optic emission spectroscopy. Tumor boron concentration peaked to therapeutically useful boron concentration values of 24-35 ppm. The boron concentration ratio tumor/normal pouch tissue ranged from 1.1 to 1.8. Pharmacokinetic curves showed that the optimum interval between BSH administration and neutron irradiation was 7-11 h. It is concluded that BNCT mediated by BSH at nuclear reactor RA-3 would be feasible.
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission-CNEA, Avenida General Paz 1499, B1650KNA, San Martin, Buenos Aires, Argentina.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Garabalino
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Heber
authors.forename: Andrea
authors.initials: A
authors.lastname: Monti Hughes
authors.forename: Sara J
authors.initials: SJ
authors.lastname: González
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Molinari
authors.forename: Emiliano C C
authors.initials: EC
authors.lastname: Pozzi
authors.forename: Susana
authors.initials: S
authors.lastname: Nievas
authors.forename: Maria E
authors.initials: ME
authors.lastname: Itoiz
authors.forename: Romina F
authors.initials: RF
authors.lastname: Aromando
authors.forename: David W
authors.initials: DW
authors.lastname: Nigg
authors.forename: William
authors.initials: W
authors.lastname: Bauer
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Trivillin
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Schwint
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001894:Borohydrides / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D002273:Carcinogens; D006224:Cricetinae; D004195:Disease Models, Animal; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D001894:Borohydrides; D002273:Carcinogens; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D015127:9,10-Dimethyl-1,2-benzanthracene