boron neutron capture therapy
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Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3421
Author(s):  
Makoto Shirakawa ◽  
Alexander Zaboronok ◽  
Kei Nakai ◽  
Yuhki Sato ◽  
Sho Kayaki ◽  
...  

Boron neutron capture therapy (BNCT) is a cancer treatment with clinically demonstrated efficacy using boronophenylalanine (BPA) and sodium mercaptododecaborate (BSH). However, tumor tissue selectivity of BSH and retention of BPA in tumor cells is a constant problem. To ensure boron accumulation and retention in tumor tissues, we designed a novel polyethylene glycol (PEG)-based boron-containing lipid (PBL) and examined the potency of delivery of boron using novel PBL-containing liposomes, facilitated by the enhanced permeability and retention (EPR) effect. PBL was synthesized by the reaction of distearoylphosphoethanolamine and BSH linked by PEG with Michael addition while liposomes modified using PBL were prepared from the mixed lipid at a constant molar ratio. In this manner, novel boron liposomes featuring BSH in the liposomal surfaces, instead of being encapsulated in the inner aqueous phase or incorporated in the lipid bilayer membrane, were prepared. These PBL liposomes also carry additional payload capacity for more boron compounds (or anticancer agents) in their inner aqueous phase. The findings demonstrated that PBL liposomes are promising candidates to effect suitable boron accumulation for BNCT.


2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Kohei Yoshimura ◽  
Hideki Kashiwagi ◽  
Shinji Kawabata ◽  
Yusuke Fukuo ◽  
Koji Takeuchi ◽  
...  

Abstract Background: High-dose methotrexate and whole brain radiation therapy (WBRT) is the recommended treatment for primary central nervous system lymphoma (PCNSL). Although the initial treatment is successful, the recurrence rate is high and the prognosis is poor. Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation that occurs when non-radioactive boron-10 is irradiated with neutrons to produce α particles (10B [n, α] 7Li). In this study, we conducted a basic research to explore the possibility of BNCT as a treatment option for PCNSL. Methods: Cellular uptake of boron using human lymphoma cell-lines after exposure to boronophenylalanine (BPA) were evaluated. The cytotoxicity of lymphoma cells by photon irradiation or neutron irradiation with BPA were also evaluated. The lymphoma cells were implanted into the mouse brain and the bio-distribution of boron after administration of BPA were measured. In neutron irradiation studies, the therapeutic effect of BNCT on mouse CNSL models were evaluated in terms of survival time. Results: The boron concentration in lymphoma cells after BPA exposure was sufficiently high, and lymphoma cells showed cytotoxicity by photon irradiation, and also by BNCT. In in vivo bio-distribution study, lymphoma cells showed enough uptake of BPA with well contrasted to the brain. In the neutron irradiation experiment, the BNCT group showed a significant prolongation in their survival time compared to the control group. Conclusions: In our study, BNCT showed its effectiveness for PCNSL in a mouse brain tumor model. PCNSL is a radio-sensitive tumor with a extremely good response rate, but it also has a high recurrence rate / a high rate of adverse events, so there is no effective treatment for recurrence after treatment. Our translational study showed that BNCT is possibly have an important role against PCNSL during the therapy lines as a new treatment option for PCNSL patients.


2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi9-vi10
Author(s):  
Motomasa Furuse ◽  
Shinji Kawabata ◽  
Masahiko Wanibuchi ◽  
Hiroyuki Shiba ◽  
Koji Takeuchi ◽  
...  

Abstract Background: Re-irradiation had a higher rate of radiation injury because recurrent MG had already irradiated in the first-line treatment. Recently, combination therapy of re-irradiation and bevacizumab showed a lower incidence of radiation injury than re-irradiation alone. Boron neutron capture therapy (BNCT), a tumor-selective particle radiation therapy, also increased radiation injury for recurrent MG, despite the greater focus on tumor cells. In this study, we evaluated the efficacy of BNCT plus bevacizumab with early induction after BNCT. Methods: Patients with recurrent MG were prospectively enrolled in this study. BNCT was performed using Kyoto University Research Reactor as a neutron source. Bevacizumab of 10 mg/kg was initiated 1–4 weeks after BNCT and was continued every 2–3 weeks until disease progression. Newly-diagnosed (de novo) glioblastoma was categorized as primary GBM (pGBM). Other MG were categorized as non-pGBM. Results: Kyoto University Research Reactor stopped irradiation for clinical use in February 2019. Twenty-five patients (14 pGBM and 11 non-pGBM) were treated with this combination therapy between June 2013 and February 2019. The median Overall survival (OS) after BNCT was 21.4 months for pGBM and 73.6 months for non-pGBM, respectively (p = 0.0428). The median progression-free survival (PFS) after BNCT was 8.3 months for pGBM and 15.6 months for non-pGBM, respectively (p = 0.0207). The objective response rate was 72 %. Alopecia occurred in all patients. Adverse events ≥ grade 3 were grade 3 proteinuria in four patients, grade 5 myocardial infarction in one patient, and grade 5 meningitis in one patient. Conclusion: BNCT plus bevacizumab showed a long OS and a long PFS, compared to our previous studies of BNCT alone for recurrent MG. Bevacizumab could provide beneficial effects not only for tumor itself, but also radiation injury. Further research with a larger sample using accelerator-based BNCT and bevacizumab is required to elucidate the efficacy and safety of this combination therapy.


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