scholarly journals TB-6 Experimental evaluation of the therapeutic potential of boron neutron capture therapy in primary central nervous system lymphoma

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Kohei Yoshimura ◽  
Hideki Kashiwagi ◽  
Shinji Kawabata ◽  
Yusuke Fukuo ◽  
Koji Takeuchi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neutron Irradiation ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Central Nervous System Lymphoma ◽  
Neutron Capture Therapy ◽  
Lymphoma Cells ◽  
Photon Irradiation ◽  
Boron Neutron Capture

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.

scholarly journals Efficacy of Boron Neutron Capture Therapy in Primary Central Nervous System Lymphoma: In Vitro and In Vivo Evaluation

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3398
Author(s):  
Kohei Yoshimura ◽  
Shinji Kawabata ◽  
Hideki Kashiwagi ◽  
Yusuke Fukuo ◽  
Koji Takeuchi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neutron Irradiation ◽  
Central Nervous System Lymphoma ◽  
Neutron Capture Therapy ◽  
Lymphoma Cells ◽  
Boron Neutron Capture ◽  
Human Lymphoma

Background: Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation method. High-dose methotrexate and whole-brain radiation therapy (WBRT) are the recommended treatments for primary central nervous system lymphoma (PCNSL). This tumor responds well to initial treatment but relapses even after successful treatment, and the prognosis is poor as there is no safe and effective treatment for relapse. In this study, we aimed to conduct basic research to explore the possibility of using BNCT as a treatment for PCNSL. Methods: The boron concentration in human lymphoma cells was measured. Subsequently, neutron irradiation experiments on lymphoma cells were conducted. A mouse central nervous system (CNS) lymphoma model was created to evaluate the biodistribution of boron after the administration of borono-phenylalanine as a capture agent. In the neutron irradiation study of a mouse PCNSL model, the therapeutic effect of BNCT on PCNSL was evaluated in terms of survival. Results: The boron uptake capability of human lymphoma cells was sufficiently high both in vitro and in vivo. In the neutron irradiation study, the BNCT group showed a higher cell killing effect and prolonged survival compared with the control group. Conclusions: A new therapeutic approach for PCNSL is urgently required, and BNCT may be a promising treatment for PCNSL. The results of this study, including those of neutron irradiation, suggest success in the conduct of future clinical trials to explore the possibility of BNCT as a new treatment option for PCNSL.

Ultrastructural Microvascular Response to Boron Neutron Capture Therapy in an Experimental Model

Neurosurgery ◽  
1989 ◽  
Vol 24 (5) ◽  
pp. 701-708 ◽  
Author(s):  
Joseph H. Goodman ◽  
John M. McGregor ◽  
Nancy R. Clendenon ◽  
Reinhard A. Gahbauer ◽  
Ralph G. Fairchild ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Model ◽  
Neutron Irradiation ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
Peritumoral Edema ◽  
Boron Neutron Capture ◽  
The Central Nervous System

ABSTRACT A CD 344 rat glioma model currently used to investigate boron neutron capture therapy (BNCT) was used to demonstrate an increased survival rate after thermal neutron irradiation enhanced by administration of 10B-enriched polyhedral borane, Na2B12H11SH. To investigate the possible effects of BNCT on normal and tumor microvasculature, we subjected animals to sublethal neutron irradiation with and without intravenous injection of 50 mg/kg of enriched 10B and performed histological and ultrastructural analyses. In the rats that did not undergo tumor transplantation, minimal detectable morphological changes in the microvasculature of the central nervous system were observed after treatment, both in the immediate posttreatment phase and at 10 months. Light microscopy of cerebral cortex and caudate nucleus showed normal cytoarchitecture with no evidence of vessel occlusion, hyalinization, thickening, or reactive gliosis. Electron microscopy demonstrated that the junctional complexes of the endothelial cells, the basal lamina, and the perivascular glia were comparable in both treated and control animals. In those animals examined at 18 months, pathological membrane-bound clusters of electron-dense vesicles were seen in pericytes. In the rats implanted with gliomas, vascular proliferation with evidence of breakdown of the blood-brain barrier and vasogenic edema occurred. In the irradiated animals, we noted increased peritumoral edema 3 days after treatment. At seven days, both increased peritumoral edema and necrosis were noted in the rats treated with BNCT. These observations show that the normal microvasculature of the central nervous system tolerates BNCT at the treatment parameters used in our experimental model; the progressive edema and necrosis found in the peritumoral region after BNCT indicate a pathological endothelial response.

scholarly journals Central nervous system tolerance to boron neutron capture therapy with p-boronophenylalanine

1997 ◽  
Vol 76 (12) ◽  
pp. 1623-1629 ◽  
Author(s):  
GM Morris ◽  
JA Coderre ◽  
PL Micca ◽  
CD Fisher ◽  
J Capala ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture

scholarly journals Synthesis and Evaluation of Dodecaboranethiol Containing Kojic Acid (KA-BSH) as a Novel Agent for Boron Neutron Capture Therapy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1551 ◽  
Author(s):  
Koji Takeuchi ◽  
Yoshihide Hattori ◽  
Shinji Kawabata ◽  
Gen Futamura ◽  
Ryo Hiramatsu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Neutron Irradiation ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Kojic Acid ◽  
Alpha Particles ◽  
Neutron Capture Therapy ◽  
Survival Times ◽  
Boron Neutron Capture ◽  
Biodistribution Studies

Boron neutron capture therapy (BNCT) is a form of tumor-cell selective particle irradiation using low-energy neutron irradiation of boron-10 (10B) to produce high-linear energy transfer (LET) alpha particles and recoiling 7Li nuclei (10B [n, alpha] 7Li) in tumor cells. Therefore, it is important to achieve the selective delivery of large amounts of 10B to tumor cells, with only small amounts of 10B to normal tissues. To develop practical materials utilizing 10B carriers, we designed and synthesized novel dodecaboranethiol (BSH)-containing kojic acid (KA-BSH). In the present study, we evaluated the effects of this novel 10B carrier on cytotoxicity, 10B concentrations in F98 rat glioma cells, and micro-distribution of KA-BSH in vitro. Furthermore, biodistribution studies were performed in a rat brain tumor model. The tumor boron concentrations showed the highest concentrations at 1 h after the termination of administration. Based on these results, neutron irradiation was evaluated at the Kyoto University Research Reactor Institute (KURRI) with KA-BSH. Median survival times (MSTs) of untreated and irradiated control rats were 29.5 and 30.5 days, respectively, while animals that received KA-BSH, followed by neutron irradiation, had an MST of 36.0 days (p = 0.0027, 0.0053). Based on these findings, further studies are warranted in using KA-BSH as a new B compound for malignant glioma.

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