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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
Authors: Futamura, Gen
Kawabata, Shinji
Nonoguchi, Naosuke
Hiramatsu, Ryo
Toho, Taichiro
Tanaka, Hiroki  kyouindb  KAKEN_id
Masunaga, Shin-Ichiro  kyouindb  KAKEN_id
Hattori, Yoshihide
Kirihata, Mitsunori
Ono, Koji
Kuroiwa, Toshihiko
Miyatake, Shin-Ichi
Author's alias: 田中, 浩基
増永, 慎一郎
小野, 公二
Keywords: Boron neutron capture therapy
F98 rat glioma model
ACBC-BSH
Issue Date: 23-Jan-2017
Publisher: Springer Nature
Journal title: Radiation Oncology
Volume: 12
Thesis number: 26
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.
Rights: © The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
URI: http://hdl.handle.net/2433/218714
DOI(Published Version): 10.1186/s13014-017-0765-4
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