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Radiat Oncol. 2017 Jan 23;12(1):26. doi: 10.1186/s13014-017-0765-4.

Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma.

Author information

1
Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.
2
Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan. neu046@osaka-med.ac.jp.
3
Kyoto university research reactor institute, 2, Asahiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, Japan.
4
Reserch Organization for the 21th Century, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Japan.
5
Division for Advanced Medical Development, Cancer Center, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.

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.

KEYWORDS:

ACBC-BSH; Boron neutron capture therapy; F98 rat glioma model

PMID:
28114947
PMCID:
PMC5260095
DOI:
10.1186/s13014-017-0765-4
[Indexed for MEDLINE]
Free PMC Article

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