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

Cells. 2021 Dec 2;10(12):3398. doi: 10.3390/cells10123398.

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.

Keywords: boron neutron capture therapy (BNCT); malignant brain tumor; primary central nervous system lymphoma (PCNSL); radiation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Boron / chemistry
  • Boron / isolation & purification
  • Boron / pharmacology
  • Boron Neutron Capture Therapy*
  • Brain / pathology
  • Brain / radiation effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / radiotherapy*
  • Cranial Irradiation
  • Disease Models, Animal
  • Humans
  • Lymphoma / drug therapy
  • Lymphoma / pathology
  • Lymphoma / radiotherapy*
  • Methotrexate / pharmacology
  • Mice
  • Phenylalanine / chemistry
  • Phenylalanine / isolation & purification
  • Phenylalanine / pharmacology
  • Tissue Distribution / drug effects

Substances

  • Phenylalanine
  • Boron
  • Methotrexate