Abstract
BackgroundBoron 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.MethodsWe 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.ResultsIn 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.ConclusionsOur findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.
Highlights
Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10
BNCT is a type of particle radiotherapy requiring lowenergy thermal neutrons and non-radioactive boron-10 (10B) compounds that can selectively accumulate in tumor cells
We developed a novel Sodium borocaptate (BSH) derivative conjugated with 1-amino3-fluorocyclobutane-1-carboxylic acid: 1-amino-3fluorocyclobutane-1-carboxylic acid (ACBC)-BSH [7], the chemical structure of which is shown Fig. 1
Summary
Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. 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. The selective destruction of tumor cells that have infiltrated normal brain is an even more difficult challenge compared with neoplasms at other organs. We have clinically applied boron neutron capture therapy (BNCT) since 2002 as an experimental adjuvant therapy for patients with recurrent or newly diagnosed malignant gliomas, and we have achieved superior outcomes compared with those of the standard treatment using fractionated photon irradiation [1, 2]. BNCT is a type of particle radiotherapy requiring lowenergy thermal neutrons and non-radioactive boron-10 (10B) compounds that can selectively accumulate in tumor cells. Fission reaction occurs neutrons are captured by 10B This results in high linear energy transfer (LET) alpha particles and recoiling lithium-7 nuclei. The biological effects of the 10B (n,α) 7Li capture reaction depends on the concentration of 10B present in the tumor cells in the neutron-irradiated field with a concomitant sparing of normal cell
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