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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
Gen Futamura; Shinji Kawabata; Naosuke Nonoguchi; Ryo Hiramatsu; Taichiro Toho; Hiroki Tanaka; Shin-Ichiro Masunaga; Yoshihide Hattori; Mitsunori Kirihata; Koji Ono; Toshihiko Kuroiwa; Shin-Ichi Miyatake; Futamura, Gen; Kawabata, Shinji; Nonoguchi, Naosuke; Hiramatsu, Ryo; Toho, Taichiro; Tanaka, Hiroki; Masunaga, Shin-Ichiro; Hattori, Yoshihide
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.
- Subjects
GLIOMA treatment; BORON; BORON-neutron capture therapy; THERAPEUTIC use of boron isotopes; CANCER radiotherapy; THERAPEUTICS; ANIMAL experimentation; BLOOD-brain barrier; BORON compounds; BRAIN tumors; COMPARATIVE studies; DRUG delivery systems; GLIOMAS; RESEARCH methodology; MEDICAL cooperation; RADIOTHERAPY; RATS; RESEARCH; SULFUR compounds; EVALUATION research; CANCER cell culture
- Publication
Radiation Oncology, 2017, Vol 12, p1
- ISSN
1748-717X
- Publication type
journal article
- DOI
10.1186/s13014-017-0765-4