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: 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
• Journal: Radiation oncology (London, England) (Radiat Oncol) Vol. 12 Issue 1 Pg. 26 (Jan 23 2017) ISSN: 1748-717X [Electronic] England
• PMID: 28114947 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Borohydrides
• Sulfhydryl Compounds
• mercaptoundecahydrododecaborate

Topics

• Animals
• Blood-Brain Barrier
• Borohydrides (chemistry, pharmacokinetics)
• Boron Neutron Capture Therapy
• Brain Neoplasms (radiotherapy)
• Drug Delivery Systems
• Glioma (radiotherapy)
• Male
• Rats
• Rats, Inbred F344
• Sulfhydryl Compounds (chemistry, pharmacokinetics)
• Tissue Distribution
• Tumor Cells, Cultured