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

Kohei Yoshimura,Minoru Suzuki,Masahiko Wanibuchi,Koji Takeuchi,Naonori Hu,Yusuke Fukuo,Takushi Takata,Shin-Ichi Miyatake,Ryo Hiramatsu,Tsubasa Watanabe,Hideki Kashiwagi,Hiroki Tanaka,Shinji Kawabata,Gen Futamura

doi:10.3390/cells10123398

Kohei Yoshimura, Minoru Suzuki + Show 12 more

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https://doi.org/10.3390/cells10123398

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Abstract

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.

Highlights

To explore the therapeutic application of Boron neutron capture therapy (BNCT) for primary central nervous system lymphoma (PCNSL), we aimed to conduct a basic study on BNCT using a human lymphoma cell line and a mouse central nervous system (CNS) lymphoma brain tumor model and to evaluate the efficacy and safety of BNCT for PCNSL
Roswell Park Memorial Institute (RPMI) 1640 medium containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin were used for cell cultures
We examined whether exposure to BPA resulted in boron uptake into the human lymphoma cells, Raji and RL

Summary

Introduction

Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation that selectively destroys tumor cells and has been clinically applied as a treatment for invasive cancers, such as high-grade meningiomas [1] and gliomas [2,3,4]. Subsequent neutron irradiation results in the capture of boron-10 (10 B) atoms by thermal neutrons to produce high linear energy transfer particles (alpha particles and 7 Li recoil nuclei). Because these particles have a short path length (5–9 μm), and their path length roughly corresponds to the size of a single tumor cell (10 μm), they only destroy B-containing cells.

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