title: Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma.
abstract: BACKGROUND
  Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate (BSH) derivative, 1-amino-3-fluorocyclobutane-1-carboxylic acid (ACBC)-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy (BNCT) of the F98 rat glioma.
  
  
  METHODS
  We evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine (BPA), in vitro and in vivo, following intravenous (i.v.) administration and intratumoral (i.t.) convection-enhanced delivery (CED) in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA/i.v., BNCT with ACBC-BSH/CED, and BNCT concomitantly using BPA/i.v. and ACBC-BSH/CED.
  
  
  RESULTS
  In vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery (CED), ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH/CED group and BPA/i.v. group of rats. The tumor/brain boron-10 concentration ratio was higher with ACBC-BSH/CED than that of BPA/i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA/i.v. and ACBC-BSH/CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant.
  
  
  CONCLUSIONS
  Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.
authors.affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Futamura
authors.affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan. neu046@osaka-med.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawabata
authors.affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.
authors.forename: Naosuke
authors.initials: N
authors.lastname: Nonoguchi
authors.affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hiramatsu
authors.affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.
authors.forename: Taichiro
authors.initials: T
authors.lastname: Toho
authors.affiliation: Kyoto university research reactor institute, 2, Asahiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Kyoto university research reactor institute, 2, Asahiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, Japan.
authors.forename: Shin-Ichiro
authors.initials: SI
authors.lastname: Masunaga
authors.affiliation: Reserch Organization for the 21th Century, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Reserch Organization for the 21th Century, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Kirihata
authors.affiliation: Kyoto university research reactor institute, 2, Asahiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kuroiwa
authors.affiliation: Division for Advanced Medical Development, Cancer Center, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Miyatake
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001894:Borohydrides / Q000737:chemistry* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016503:Drug Delivery Systems; D005910:Glioma / Q000532:radiotherapy*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate
keywords: ACBC-BSH; Boron neutron capture therapy; F98 rat glioma model