Abstract
Simple SummaryWe have developed a new boron compound for application in boron neutron capture therapy (BNCT) named boronophenylalanine–amide alkyl dodecaborate (BADB). It is characterized by a larger amount of 10B per molecule, linking boronphenylalanine (BPA) and dodecaborate, and we conducted various experiments on its efficacy. Its high accumulation at the cellular level made it a promising novel drug, but it did not sufficiently accumulate in brain tumor tissue when intravenously administered. However, in neutron irradiation experiments, the drug showed remarkably high compound biological effectiveness and significantly prolonged the survival time in rat brain tumor models. We confirmed the antitumor efficacy of BADB in BNCT and its additional efficacy when administered in combination with BPA. Though this drug showed poor results when administered as a single agent, it was superior to BPA alone when administered in combination with BPA, making it a drug that we have been waiting for in our clinical practice.Background: The development of effective boron compounds is a major area of research in the study of boron neutron capture therapy (BNCT). We created a novel boron compound, boronophenylalanine–amide alkyl dodecaborate (BADB), for application in BNCT and focused on elucidating how it affected a rat brain tumor model. Methods: The boron concentration of F98 rat glioma cells following exposure to boronophenylalanine (BPA) (which is currently being utilized clinically) and BADB was evaluated, and the biodistributions in F98 glioma-bearing rats were assessed. In neutron irradiation studies, the in vitro cytotoxicity of each boron compound and the in vivo corresponding therapeutic effect were evaluated in terms of survival time. Results: The survival fractions of the groups irradiated with BPA and BADB were not significantly different. BADB administered for 6 h after the termination of convection-enhanced delivery ensured the highest boron concentration in the tumor (45.8 μg B/g). The median survival time in the BADB in combination with BPA group showed a more significant prolongation of survival than that of the BPA group. Conclusion: BADB is a novel boron compound for BNCT that triggers a prolonged survival effect in patients receiving BNCT.
Highlights
Boron neutron capture therapy (BNCT) is a type of particle treatment that selectively destroys tumor cells that has been clinically applied to invasive cancers such as high-grade glioma [1,2,3], meningioma [4], melanoma [5], and head and neck cancer [6]
The cellular boron concentrations obtained using BPA and boronophenylalanine–amide alkyl dodecaborate (BADB), incubated with 5 and 20 μg B/mL are shown in Figure 2A–C, respectively
In 10 μg B/mL of each boron compound, BPA and BADB showed no significant differences in concentration at all incubation times (43.6 ± 4.2, 48.0 ± 5.4, and 52.8 ± 2.2 μg B/109 cells for BPA vs. 51.6 ± 5.0, 46.4 ± 1.1, and 53.4 ± 4.7 μg B/109 cells for BADB)
Summary
Boron neutron capture therapy (BNCT) is a type of particle treatment that selectively destroys tumor cells that has been clinically applied to invasive cancers such as high-grade glioma [1,2,3], meningioma [4], melanoma [5], and head and neck cancer [6]. Particles (α particles and 7 Li recoil nuclei) Since these particles have a short path length (5–9 μm) and their path length approximately corresponds to the size of one tumor cell (10 μm), their disruptive effects are limited to boron-containing cells. The in vitro cytotoxicity of each boron compound and the in vivo corresponding therapeutic effect were evaluated in terms of survival time
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
