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Importance of radiobiological studies for the advancement of boron neutron capture therapy (BNCT)

Part of: Advancements in the radiobiology of low and high-LET radiation

Published online by Cambridge University Press:  31 March 2022

Andrea Monti Hughes Open the ORCID record for Andrea Monti Hughes [Opens in a new window]
Andrea Monti Hughes*
Affiliation:
Division of Radiation Pathology, Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires, Argentina National Research Council (CONICET), Buenos Aires, Argentina
*
Author for correspondence: Andrea Monti Hughes, E-mail: [email protected]
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Abstract

Boron neutron capture therapy (BNCT) is a tumour selective particle radiotherapy, based on the administration of boron carriers incorporated preferentially by tumour cells, followed by irradiation with a thermal or epithermal neutron beam. BNCT clinical results to date show therapeutic efficacy, associated with an improvement in patient quality of life and prolonged survival. Translational research in adequate experimental models is necessary to optimise BNCT for different pathologies. This review recapitulates some examples of BNCT radiobiological studies for different pathologies and clinical scenarios, strategies to optimise boron targeting, enhance BNCT therapeutic effect and minimise radiotoxicity. It also describes the radiobiological mechanisms induced by BNCT, and the importance of the detection of biomarkers to monitor and predict the therapeutic efficacy and toxicity of BNCT alone or combined with other strategies. Besides, there is a brief comment on the introduction of accelerator-based neutron sources in BNCT. These sources would expand the clinical BNCT services to more patients, and would help to make BNCT a standard treatment modality for various types of cancer. Radiobiological BNCT studies have been of utmost importance to make progress in BNCT, being essential to design novel, safe and effective clinical BNCT protocols.

Keywords

Accelerator-based neutron sourcesBNCTBNCT-induced mechanismsboron neutron capture therapycancerradiobiological studiesstrategies
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 24 , 2022 , e14
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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References

Coderre, JA and Morris, GM (1999) The radiation biology of boron neutron capture therapy. Radiation Research 151, 1–18.CrossRefGoogle ScholarPubMed
Suzuki, M (2020) Boron neutron capture therapy (BNCT): a unique role in radiotherapy with a view to entering the accelerator-based BNCT era. International Journal of Clinical Oncology 25, 43–50.CrossRefGoogle ScholarPubMed
Matsumoto, Y et al. (2021) A critical review of radiation therapy: from particle beam therapy (proton, carbon, and BNCT) to beyond. Journal of Personalised Medicine 11, 825.CrossRefGoogle Scholar
Barth, RF et al. (2005) Boron neutron capture therapy of cancer: current status and future prospects. Clinical Cancer Research 11, 3987–4002.CrossRefGoogle ScholarPubMed
Hopewell, JW et al. (2011) The radiobiological principles of boron neutron capture therapy: a critical review. Applied Radiation and Isotopes 69, 1756–1759.CrossRefGoogle ScholarPubMed
Pozzi, EC et al. (2012) Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model. Radiation and Environmental Biophysics 51, 331–339CrossRefGoogle Scholar
Monti Hughes, A et al. (2009) Boron neutron capture therapy (BNCT) inhibits tumour development from precancerous tissue: an experimental study that supports a potential new application of BNCT. Applied Radiation and Isotopes 67(7–8 Suppl), S313–S317.CrossRefGoogle ScholarPubMed
Schwint, AE et al. (2018) Translational radiobiological boron neutron capture therapy (BNCT) studies for the treatment of different pathologies: a bench to bedside approach. Austin Journal of Nanomedicine & Nanotechnology 6, 1049.Google Scholar
Schwint, AE et al. (2019) Teachings of our translational studies on boron neutron capture therapy (BNCT): thinking ‘outside the box’. Therapeutic Radiology and Oncology 3, 20.CrossRefGoogle Scholar
González, SJ et al. (2004) First BNCT treatment of a skin melanoma in Argentina: dosimetric analysis and clinical outcome. Applied Radiation and Isotopes 61, 1101–1105.CrossRefGoogle ScholarPubMed
Kankaanranta, L et al. (2012) Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer: final analysis of a phase I/II trial. International Journal of Radiation Oncology, Biology, Physics 82, e67–e75.CrossRefGoogle ScholarPubMed
Miyatake, S et al. (2014) Boron neutron capture therapy with bevacizumab may prolong the survival of recurrent malignant glioma patients: four cases. Radiation Oncology 9, 6.CrossRefGoogle ScholarPubMed
Hiratsuka, J et al. (2018) Boron neutron capture therapy for vulvar melanoma and genital extramammary Paget's disease with curative responses. Cancer Communications 38, 38.CrossRefGoogle ScholarPubMed
Wang, LW et al. (2018) Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua open pool reactor. Cancer Communications 38, 37.CrossRefGoogle ScholarPubMed
Chen, YW et al. (2021) Salvage boron neutron capture therapy for malignant brain tumour patients in compliance with emergency and compassionate use: evaluation of 34 cases in Taiwan. Biology 10, 334.CrossRefGoogle Scholar
Porra, L et al. (2022) Accelerator-based boron neutron capture therapy facility at the Helsinki university hospital. Acta Oncologica 61(2), 269–273. https://doi.org/10.1080/0284186X.2021.1979646.CrossRefGoogle ScholarPubMed
Miyatake, SI et al. (2020) Boron neutron capture therapy for malignant brain tumours. Journal of Neuro-Oncology 149, 1–11.CrossRefGoogle Scholar
Garabalino, MA et al. (2011) Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model. Radiation and Environmental Biophysics 50, 199–207.CrossRefGoogle Scholar
Schwint, AE and Trivillin, VA (2015) ‘Close-to-ideal’ tumour boron targeting for boron neutron capture therapy is possible with ‘less-than-ideal’ boron carriers approved for use in humans. Therapeutic Delivery 6, 269–272.CrossRefGoogle ScholarPubMed
Portu, A et al. (2015) Neutron autoradiography to study boron compound microdistribution in an oral cancer model. International Journal of Radiation Biology 91, 329–335.CrossRefGoogle Scholar
Ono, K et al. (2000) The combined effect of electroporation and borocaptate in boron neutron capture therapy for murine solid tumours. Japanese Journal of Cancer Research: Gann 91, 853–858.CrossRefGoogle Scholar
Wada, Y et al. (2018) Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy. Journal of Radiation Research 59, 122–128.CrossRefGoogle ScholarPubMed
Barth, RF et al. (2004) Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent. Applied Radiation and Isotopes 61, 899–903.CrossRefGoogle Scholar
Heber, EM et al. (2014) Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model. Proceedings of the National Academy of Sciences of the United States of America 111, 16077–16081.CrossRefGoogle ScholarPubMed
Oleshkevich, E et al. (2019) Combining magnetic nanoparticles and icosahedral boron clusters in biocompatible inorganic nanohybrids for cancer therapy. Nanomedicine: Nanotechnology, Biology, and Medicine 20, 101986.CrossRefGoogle ScholarPubMed
Torresan, V et al. (2021) Biocompatible iron–boron nanoparticles designed for neutron capture therapy guided by magnetic resonance imaging. Advanced Healthcare Materials 10, e2001632.CrossRefGoogle ScholarPubMed
Ban, HS and Nakamura, H (2015) Boron-based drug design. Chemical Record 15, 616–635.CrossRefGoogle ScholarPubMed
Kawai, K et al. (2020) Cyclic RGD-functionalized closo-dodecaborate albumin conjugates as integrin targeting boron carriers for neutron capture therapy. Molecular Pharmaceutics 17, 3740–3747.CrossRefGoogle ScholarPubMed
Couto, M et al. (2020) Bimodal therapeutic agents against glioblastoma, One of the most lethal forms of cancer. Chemistry (Weinheim an der Bergstrasse, Germany) 26, 14335–14340.Google ScholarPubMed
Nuez-Martinez, M et al. (2021) Cobaltabis(dicarbollide) ([o-COSAN]−) as multifunctional chemotherapeutics: a prospective application in boron neutron capture therapy (BNCT) for glioblastoma. Cancers 13, 6367.CrossRefGoogle ScholarPubMed
Endo, Y et al. (2001) Potent estrogen agonists based on carborane as a hydrophobic skeletal structure. A new medicinal application of boron clusters. Chemistry & Biology 8, 341–355.CrossRefGoogle ScholarPubMed
Poater, J et al. (2014) π aromaticity and three-dimensional aromaticity: two sides of the same coin? Angewandte Chemie (International Ed. in English) 53, 12191–12195.CrossRefGoogle ScholarPubMed
Poater, J et al. (2020) Too persistent to give up: aromaticity in boron clusters survives radical structural changes. Journal of the American Chemical Society 142, 9396–9407.CrossRefGoogle ScholarPubMed
Ferrari, E et al. (2019) Urinary proteomics profiles are useful for detection of cancer biomarkers and changes induced by therapeutic procedures. Molecules (Basel, Switzerland) 24, 794.CrossRefGoogle ScholarPubMed
Sauerwein, W et al. (2021) Theranostics in boron neutron capture therapy. Life (Basel, Switzerland) 11, 330.Google ScholarPubMed
Scott, JG et al. (2021) Pan-cancer prediction of radiotherapy benefit using genomic-adjusted radiation dose (GARD): a cohort-based pooled analysis. The Lancet. Oncology 22, 1221–1229.CrossRefGoogle ScholarPubMed
Watanabe, T et al. (2016) Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy. BMC Cancer 16, 859.CrossRefGoogle ScholarPubMed
Li, J et al. (2019) A metabolically stable boron-derived tyrosine serves as a theranostic agent for positron emission tomography guided boron neutron capture therapy. Bioconjugate Chemistry 30, 2870–2878.CrossRefGoogle ScholarPubMed
Kalot, G et al. (2020) Aza-BODIPY: a new vector for enhanced theranostic boron neutron capture therapy applications. Cells 9, 1953.CrossRefGoogle ScholarPubMed
Varadarajan, A et al. (1991) Conjugation of phenyl isothiocyanate derivatives of carborane to antitumor antibody and in vivo localization of conjugates in nude mice. Bioconjugate Chemistry 2, 102–110.CrossRefGoogle ScholarPubMed
Armstrong, AF and Valliant, JF (2007) The bioinorganic and medicinal chemistry of carboranes: from new drug discovery to molecular imaging and therapy. Dalton Transactions (Cambridge, England: 2003) 38, 4240–4251.CrossRefGoogle Scholar
Teixidor, F and Viñas, C (2018) Chapter 5: Halogenated icosahedral carboranes: a platform for remarkable applications. In Hosman, NS (Northern Illinois University, USA) and Eagling, R (eds), Handbook of Boron Science. World Scientific, vol. 1, pp. 205–228, https://doi.org/10.1142/9781786344649_0005.CrossRefGoogle Scholar
Sato, A et al. (2015) Proteomic analysis of cellular response induced by boron neutron capture reaction in human squamous cell carcinoma SAS cells. Applied Radiation and Isotopes 106, 213–219.CrossRefGoogle ScholarPubMed
Rodriguez, C et al. (2018) In vitro studies of DNA damage and repair mechanisms induced by BNCT in a poorly differentiated thyroid carcinoma cell line. Radiation and Environmental Biophysics 57, 143–152.CrossRefGoogle Scholar
Kreimann, EL et al. (2001) Boron neutron capture therapy for the treatment of oral cancer in the hamster cheek pouch model. Cancer Research 61, 8638–8642.Google ScholarPubMed
Takahara, K et al. (2015) The anti-proliferative effect of boron neutron capture therapy in a prostate cancer xenograft model. PLoS One 10, e0136981.CrossRefGoogle Scholar
Hung, YH et al. (2019) Therapeutic efficacy and radiobiological effects of boric acid-mediated BNCT in a VX2 multifocal liver tumour-bearing rabbit model. Anticancer Research 39, 5495–5504.CrossRefGoogle Scholar
Andoh, T et al. (2020) Preclinical study of boron neutron capture therapy for bone metastasis using human breast cancer cell lines. Applied Radiation and Isotopes 165, 109257.CrossRefGoogle ScholarPubMed
Hawthorne, MF and Lee, MW (2003) A critical assessment of boron target compounds for boron neutron capture therapy. Journal of Neuro-Oncology 62, 33–45.CrossRefGoogle ScholarPubMed
Nomoto, T et al. (2020) Poly(vinyl alcohol) boosting therapeutic potential of p-boronophenylalanine in neutron capture therapy by modulating metabolism. Science Advances 6, eaaz1722.CrossRefGoogle ScholarPubMed
Fujii, H et al. (2011) Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumours in vivo. Radiation Oncology (London, England) 6, 8.CrossRefGoogle Scholar
Sasai, M et al. (2016) Novel hyaluronan formulation enhances the efficacy of boron neutron capture therapy for murine mesothelioma. Anticancer Research 36, 907–911.Google ScholarPubMed
Sun, T et al. (2016) Targeting glioma stem cells enhances anti-tumour effect of boron neutron capture therapy. Oncotarget 7, 43095–43108.CrossRefGoogle Scholar
Yanagie, H et al. (2020) Single-dose toxicity study by intra-arterial injection of 10BSH entrapped water-in-oil-in-water emulsion for boron neutron capture therapy to hepatocellular carcinoma. Applied Radiation and Isotopes 163, 109202.CrossRefGoogle ScholarPubMed
Yanagie, H et al. (2021) Suppression of tumour growth in a rabbit hepatic cancer model by boron neutron capture therapy with liposomal boron delivery systems. In Vivo (Athens, Greece) 35, 3125–3135.Google Scholar
Ono, K et al. (1999) The combined effect of boronophenylalanine and borocaptate in boron neutron capture therapy for SCCVII tumours in mice. International Journal of Radiation Oncology, Biology, Physics 43, 431–436.CrossRefGoogle ScholarPubMed
Barth, RF et al. (2003) Rat brain tumour models to assess the efficacy of boron neutron capture therapy: a critical evaluation. Journal of Neuro-Oncology 62, 61–74.CrossRefGoogle ScholarPubMed
Trivillin, VA et al. (2006) Therapeutic success of boron neutron capture therapy (BNCT) mediated by a chemically non-selective boron agent in an experimental model of oral cancer: a new paradigm in BNCT radiobiology. Radiation Research 166, 387–396.CrossRefGoogle Scholar
Molinari, AJ et al. (2011) ‘Sequential’ boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model. Radiation Research 175, 463–472.CrossRefGoogle ScholarPubMed
Monti Hughes, A et al. (2011) Boron neutron capture therapy (BNCT) in an oral precancer model: therapeutic benefits and potential toxicity of a double application of BNCT with a six-week interval. Oral Oncology 47, 1017–1022.CrossRefGoogle Scholar
Monti Hughes, A et al. (2013) Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model. Oral Diseases 19, 789–795.CrossRefGoogle Scholar
Monti Hughes, A et al. (2019) Different oral cancer scenarios to personalise targeted therapy: boron neutron capture therapy translational studies. Therapeutic Delivery 10, 353–362.CrossRefGoogle Scholar
Monti Hughes, A et al. (2015) Histamine reduces boron neutron capture therapy-induced mucositis in an oral precancer model. Oral Diseases 21, 770–777.CrossRefGoogle Scholar
Koning, GA et al. (2004) Targeting liposomes to tumour endothelial cells for neutron capture therapy. Applied Radiation and Isotopes 61, 963–967.CrossRefGoogle ScholarPubMed
Kang, W et al. (2017) Cyclic-RGDyC functionalized liposomes for dual-targeting of tumour vasculature and cancer cells in glioblastoma: an in vitro boron neutron capture therapy study. Oncotarget 8, 36614–36627.CrossRefGoogle Scholar
Ono, K et al. (1998) Effects of boron neutron capture therapy using borocaptate sodium in combination with a tumour-selective vasoactive agent in mice. Japanese Journal of Cancer Research: Gann 89, 334–340.CrossRefGoogle Scholar
Masunaga, S et al. (2004) Combination of the vascular targeting agent ZD6126 with boron neutron capture therapy. International Journal of Radiation Oncology, Biology, Physics 60, 920–927.CrossRefGoogle ScholarPubMed
Yoneyama, T et al. (2021) Tumour vasculature-targeted 10B delivery by an annexin A1-binding peptide boosts effects of boron neutron capture therapy. BMC Cancer 21, 72.CrossRefGoogle ScholarPubMed
Molinari, AJ et al. (2012) Tumour blood vessel ‘normalization’ improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer. Radiation Research 177, 59–68.CrossRefGoogle Scholar
Molinari, AJ et al. (2015) Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels. Acta Oncologica (Stockholm, Sweden) 54, 99–106.CrossRefGoogle Scholar
Garabalino, MA et al. (2019) Electroporation optimizes the uptake of boron-10 by tumour for boron neutron capture therapy (BNCT) mediated by GB-10: a boron biodistribution study in the hamster cheek pouch oral cancer model. Radiation and Environmental Biophysics 58, 455–467.CrossRefGoogle ScholarPubMed
Yamatomo, N et al. (2013) Sonoporation as an enhancing method for boron neutron capture therapy for squamous cell carcinomas. Radiation Oncology (London, England) 8, 280.CrossRefGoogle ScholarPubMed
Lin, YC et al. (2021) The effect of low-dose gamma irradiation on the uptake of boronophenylalanine to enhance the efficacy of boron neutron capture therapy in an orthotopic oral cancer model. Radiation Research 195, 347–354.CrossRefGoogle Scholar
Barth, RF et al. (2000) Boron neutron capture therapy of brain tumours: enhanced survival and cure following blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine. International Journal of Radiation Oncology, Biology, Physics 47, 209–218.CrossRefGoogle ScholarPubMed
Futamura, G et al. (2017) Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma. Radiation Oncology (London, England) 12, 26.CrossRefGoogle ScholarPubMed
Joel, DD et al. (1999) Effect of dose and infusion time on the delivery of p-boronophenylalanine for neutron capture therapy. Journal of Neuro-Oncology 41, 213–221.CrossRefGoogle ScholarPubMed
Ono, K et al. (2006). Neutron irradiation under continuous BPA injection for solving the problem of heterogeneous distribution of BPA, Proceeding 12th International Conference on Neutron Capture Therapy. Takamatsu, Japan, 27–30.Google Scholar
Barth, RF et al. (2004) Combination of boron neutron capture therapy and external beam radiotherapy for brain tumours. International Journal of Radiation Oncology, Biology, Physics 58, 267–277.CrossRefGoogle Scholar
Ohnishi, K et al. (2021) Enhancement of cancer cell-killing effects of boron neutron capture therapy by manipulating the expression of L-type amino acid transporter 1. Radiation Research 196, 17–22.CrossRefGoogle ScholarPubMed
Capuani, S et al. (2009) Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading. Applied Radiation and Isotopes 67(7–8 Suppl), S34–S36.CrossRefGoogle ScholarPubMed
Watanabe, T et al. (2016) L-Phenylalanine preloading reduces the (10)B(n,α)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours. Cancer Letters 370, 27–32.CrossRefGoogle Scholar
Kondo, N et al. (2020) Glioma stem-like cells can be targeted in boron neutron capture therapy with boronophenylalanine. Cancers 12, 3040.CrossRefGoogle ScholarPubMed
Kinashi, Y et al. (2001) Sensitizing effect of the phosphatidylinositol 3-kinase inhibitor wortmannin on thermal neutron irradiation with or without boron compound. Radiation Medicine 19, 27–32.Google ScholarPubMed
Qi, P et al. (2020) The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT). Biomaterials Science 8, 2778–2785.CrossRefGoogle Scholar
Perona, M et al. (2013) Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma. Radiation and Environmental Biophysics 52, 363–373.CrossRefGoogle ScholarPubMed
Conway-Kenny, R et al. (2021) Ru(II) and Ir(III) phenanthroline-based photosensitisers bearing o-carborane: PDT agents with boron carriers for potential BNCT. Biomaterials Science 9, 5691–5702.CrossRefGoogle ScholarPubMed
Tatebe, H et al. (2020) Effect of rapamycin on the radio-sensitivity of cultured tumour cells following boron neutron capture reaction. World Journal of Oncology 11, 158–164.CrossRefGoogle ScholarPubMed
Bakeine, GJ et al. (2009) Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases. Applied Radiation and Isotopes 67(7–8 Suppl), S332–S335.CrossRefGoogle Scholar
Farías, RO et al. (2015) Toward a clinical application of ex situ boron neutron capture therapy for lung tumours at the RA-3 reactor in Argentina. Medical Physics 42, 4161–4173.CrossRefGoogle Scholar
Andoh, T et al. (2015) Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: trial using a lung metastasis model of CCS. Applied Radiation and Isotopes 106, 195–201.CrossRefGoogle ScholarPubMed
Trivillin, VA et al. (2019) Translational boron neutron capture therapy (BNCT) studies for the treatment of tumours in lung. International Journal of Radiation Biology 95, 646–654.CrossRefGoogle ScholarPubMed
Masunaga, SI et al. (2014) Effect of bevacizumab combined with boron neutron capture therapy on local tumour response and lung metastasis. Experimental and Therapeutic Medicine 8, 291–301.CrossRefGoogle ScholarPubMed
Masunaga, SI et al. (2019) Usefulness of combination with both continuous administration of hypoxic cytotoxin and mild temperature hyperthermia in boron neutron capture therapy in terms of local tumour response and lung metastatic potential. International Journal of Radiation Biology 95, 1708–1717.CrossRefGoogle ScholarPubMed
Trivillin, VA et al. (2017) Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer. Radiation and Environmental Biophysics 56, 365–375.CrossRefGoogle Scholar
Trivillin, VA et al. (2021) Evaluation of local, regional and abscopal effects of boron neutron capture therapy (BNCT) combined with immunotherapy in an ectopic colon cancer model. The British Journal of Radiology 94(1128), 20210593. https://doi.org/10.1259/bjr.20210593.CrossRefGoogle Scholar
Kinashi, Y et al. (2007) Evaluation of micronucleus induction in lymphocytes of patients following boron-neutron-capture-therapy: a comparison with thyroid cancer patients treated with radioiodine. Journal of Radiation Research 48, 197–204.CrossRefGoogle ScholarPubMed
Aromando, RF et al. (2010) Early effect of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) on mast cells in premalignant tissue and tumours of the hamster cheek pouch. Oral Oncology 46, 355–359.CrossRefGoogle ScholarPubMed
Khan, AA et al. (2019) BNCT induced immunomodulatory effects contribute to mammary tumour inhibition. PLoS One 14, e0222022.CrossRefGoogle Scholar
Trivillin, VA et al. (2016) Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: radiobiological studies at RA-1 Nuclear Reactor in a model of antigen-induced arthritis in rabbits. Radiation and Environmental Biophysics 55, 467–475.CrossRefGoogle Scholar
Kraft, SL et al. (1992) Borocaptate sodium: a potential boron delivery compound for boron neutron capture therapy evaluated in dogs with spontaneous intracranial tumours. Proceedings of the National Academy of Sciences of the United States of America 89, 11973–11977.CrossRefGoogle Scholar
Dagrosa, MA et al. (2004) Biodistribution of p-borophenylalanine (BPA) in dogs with spontaneous undifferentiated thyroid carcinoma (UTC). Applied Radiation and Isotopes 61, 911–915.CrossRefGoogle Scholar
Mitin, VN et al. (2009) Comparison of BNCT and GdNCT efficacy in treatment of canine cancer. Applied Radiation and Isotopes 67(7-8 Suppl), S299–S301.CrossRefGoogle ScholarPubMed
Takeuchi, A (1985) Possible application of boron neutron capture therapy to canine osteosarcoma. Nihon Juigaku Zasshi. The Japanese Journal of Veterinary Science 47, 869–878.Google ScholarPubMed
Rao, M et al. (2004) BNCT of 3 cases of spontaneous head and neck cancer in feline patients. Applied Radiation and Isotopes 61, 947–952.CrossRefGoogle ScholarPubMed
Trivillin, VA et al. (2008) Boron neutron capture therapy (BNCT) for the treatment of spontaneous nasal planum squamous cell carcinoma in felines. Radiation and Environmental Biophysics 47, 147–155.CrossRefGoogle ScholarPubMed
Schwint, AE et al. (2020) Clinical veterinary boron neutron capture therapy (BNCT) studies in dogs with head and neck cancer: bridging the gap between translational and clinical studies. Biology 9, 327.CrossRefGoogle ScholarPubMed
Zhou, C and Parsons, JL (2020) The radiobiology of HPV-positive and HPV-negative head and neck squamous cell carcinoma. Expert Reviews in Molecular Medicine 22, e3.CrossRefGoogle ScholarPubMed
Okamoto, E et al. (2015) Detection of DNA double-strand breaks in boron neutron capture reaction. Applied Radiation and Isotopes 106, 185–188.CrossRefGoogle ScholarPubMed
Maliszewska-Olejniczak, K et al. (2021) Molecular mechanisms of specific cellular DNA damage response and repair induced by the mixed radiation field during boron neutron capture therapy. Frontiers in Oncology 11, 676575.CrossRefGoogle ScholarPubMed
Dymova, MA et al. (2020) Boron neutron capture therapy: current status and future perspectives. Cancer Communications (London, England) 40, 406–421.CrossRefGoogle ScholarPubMed
Kinashi, Y et al. (2011) DNA double-strand break induction in Ku80-deficient CHO cells following boron neutron capture reaction. Radiation Oncology (London, England) 6, 106.CrossRefGoogle ScholarPubMed
Seki, K et al. (2015) Influence of p53 status on the effects of boron neutron capture therapy in glioblastoma. Anticancer Research 35, 169–174.Google ScholarPubMed
Masunaga, S et al. (2016) Effect of oxygen pressure during incubation with a (10)B-carrier on (10)B uptake capacity of cultured p53 wild-type and mutated tumour cells: dependency on p53 status of tumour cells and typesof (10)B-carriers. International Journal of Radiation Biology 92, 187–194.CrossRefGoogle Scholar
Chen, KH et al. (2019) Analysis of DNA damage responses after boric acid-mediated boron neutron capture therapy in hepatocellular carcinoma. Anticancer Research 39, 6661–6671.CrossRefGoogle ScholarPubMed
Fujita, Y et al. (2011) Induction of multinucleation in oral squamous cell carcinoma tissue with mutated p53 surviving boron neutron capture therapy. International Journal of Radiation Biology 87, 293–301.CrossRefGoogle ScholarPubMed
Jamsranjav, E et al. (2019) DNA strand breaks induced by fast and thermal neutrons from YAYOI research reactor in the presence and absence of boric acid. Radiation Research 191, 483–489.CrossRefGoogle ScholarPubMed
Oliveira, NG et al. (2001) Evaluation of the genotoxic effects of the boron neutron capture reaction in human melanoma cells using the cytokinesis block micronucleus assay. Mutagenesis 16, 369–375.CrossRefGoogle ScholarPubMed
Dagrosa, A et al. (2011) Studies for the application of boron neutron capture therapy to the treatment of differentiated thyroid cancer. Applied Radiation and Isotopes 69, 1752–1755.CrossRefGoogle Scholar
Kondo, N et al. (2016a) DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV. Radiation and Environmental Biophysics 55, 89–94.CrossRefGoogle Scholar
Kondo, N et al. (2016b) Detection of γH2AX foci in mouse normal brain and brain tumour after boron neutron capture therapy. Reports of Practical Oncology and Radiotherapy 21, 108–112.CrossRefGoogle Scholar
Masutani, M et al. (2014) Histological and biochemical analysis of DNA damage after BNCT in rat model. Applied Radiation and Isotopes 88, 104–108.CrossRefGoogle ScholarPubMed
Scott, JG et al. (2017) A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. The Lancet. Oncology 18, 202–211. Erratum in: The Lancet Oncology 2017;18(2),e65.CrossRefGoogle ScholarPubMed
Fujita, Y et al. (2009) Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma. Radiation Oncology (London, England) 4, 63.CrossRefGoogle ScholarPubMed
Kinashi, Y et al. (2020) The combined effect of neutron irradiation and temozolomide on glioblastoma cell lines with different MGMT and p53 status. Applied Radiation and Isotopes 163, 109204.CrossRefGoogle ScholarPubMed
Faião-Flores, F et al. (2013) Apoptosis through Bcl-2/Bax and cleaved caspase up-regulation in melanoma treated by boron neutron capture therapy. PLoS One 8, e59639.CrossRefGoogle ScholarPubMed
Faião-Flores, F et al. (2013) Cell cycle arrest, extracellular matrix changes and intrinsic apoptosis in human melanoma cells are induced by boron neutron capture therapy. Toxicology in Vitro 27, 1196–1204.CrossRefGoogle ScholarPubMed
Masunaga, S et al. (2001) Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumours. International Journal of Radiation Oncology, Biology, Physics 51, 828–839.CrossRefGoogle Scholar
Masunaga, S et al. (2002) Impact of the p53 status of the tumour cells on the effect of reactor neutron beam irradiation, with emphasis on the response of intratumour quiescent cells. Japanese Journal of Cancer Research: Gann 93, 1366–1377.CrossRefGoogle Scholar
Dagrosa, MA et al. (2007) Optimization of boron neutron capture therapy for the treatment of undifferentiated thyroid cancer. International Journal of Radiation Oncology, Biology, Physics 69, 1059–1066.CrossRefGoogle ScholarPubMed
Perona, M et al. (2011) In vitro studies of cellular response to DNA damage induced by boron neutron capture therapy. Applied Radiation and Isotopes 69, 1732–1736.CrossRefGoogle ScholarPubMed
Wang, P et al. (2010) Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax. BMC Cancer 10, 661.CrossRefGoogle ScholarPubMed
Kamida, A et al. (2008) Effect of neutron capture therapy on the cell cycle of human squamous cell carcinoma cells. International Journal of Radiation Biology 84, 191–199.CrossRefGoogle ScholarPubMed
Sun, T et al. (2013) Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro. Radiation Oncology (London, England) 8, 195.CrossRefGoogle ScholarPubMed
Masunaga, S et al. (2010) Evaluation of the radiosensitivity of the oxygenated tumour cell fractions in quiescent cell populations within solid tumours. Radiation Research 174, 459–466.CrossRefGoogle Scholar
Kamida, A et al. (2006) Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model. International Journal of Radiation Biology 82, 21–29.CrossRefGoogle Scholar
Aromando, RF et al. (2009) Insight into the mechanisms underlying tumour response to boron neutron capture therapy in the hamster cheek pouch oral cancer model. Journal of Oral Pathology & Medicine 38, 448–454.CrossRefGoogle ScholarPubMed
Jing, X et al. (2019) Role of hypoxia in cancer therapy by regulating the tumour microenvironment. Molecular Cancer 18, 157.CrossRefGoogle Scholar
Yoshida, F et al. (2002) Cell cycle dependence of boron uptake from two boron compounds used for clinical neutron capture therapy. Cancer Letters 187, 135–141. Erratum in: Cancer letters, 2004;207(2),251. Erratum in: Cancer Letters, 2005;218(2),235.CrossRefGoogle ScholarPubMed
Masunaga, S et al. (2013) Radiosensitivity of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction. The British Journal of Radiology 86, 20120302.CrossRefGoogle ScholarPubMed
Masunaga, S and Ono, K (2002) Significance of the response of quiescent cell populations within solid tumours in cancer therapy. Journal of Radiation Research 43, 11–25.CrossRefGoogle ScholarPubMed
Masunaga, S et al. (2012) Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy. The British Journal of Radiology 85, 249–258.CrossRefGoogle Scholar
Harada, T et al. (2020) YC-1 sensitizes the antitumour effects of boron neutron capture therapy in hypoxic tumour cells. Journal of Radiation Research 61, 524–534.CrossRefGoogle Scholar
Sanada, Y et al. (2021) HIF-1α affects sensitivity of murine squamous cell carcinoma to boron neutron capture therapy with BPA. International Journal of Radiation Biology 97, 1441–1449.CrossRefGoogle ScholarPubMed
Kinashi, Y et al. (2007) A bystander effect observed in boron neutron capture therapy: a study of the induction of mutations in the HPRT locus. International Journal of Radiation Oncology, Biology, Physics 68, 508–514.CrossRefGoogle ScholarPubMed
Kinashi, Y et al. (2009). Bystander effect-induced mutagenicity in HPRT locus of CHO cells following BNCT neutron irradiation: characteristics of point mutations by sequence analysis. Applied Radiation and Isotopes 67(7-8 Suppl), S325–S327.CrossRefGoogle ScholarPubMed
Kinashi, Y et al. (2004) Ascorbic acid reduced mutagenicity at the HPRT locus in CHO cells against thermal neutron radiation. Applied Radiation and Isotopes 61, 929–932.CrossRefGoogle Scholar
Kondo, N et al. (2017) Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma. Journal of Neuro-Oncology 133, 107–118.CrossRefGoogle ScholarPubMed
Tilborghs, S et al. (2017) The role of nuclear factor-kappa B signaling in human cervical cancer. Critical Reviews in Oncology/Hematology 120, 141–150.CrossRefGoogle ScholarPubMed
Porras, I et al. (2020) BNCT research activities at the Granada group and the project NeMeSis: neutrons for medicine and sciences, towards an accelerator-based facility for new BNCT therapies, medical isotope production and other scientific neutron applications. Applied Radiation and Isotopes 165, 109247.CrossRefGoogle Scholar
Cartelli, DE et al. (2020) Status of low-energy accelerator-based BNCT worldwide and in Argentina. Applied Radiation and Isotopes 166, 109315.CrossRefGoogle ScholarPubMed
Sato, E et al. (2018) Radiobiological response of U251MG, CHO-K1 and V79 cell lines to accelerator-based boron neutron capture therapy. Journal of Radiation Research 59, 101–107.CrossRefGoogle ScholarPubMed
Wang, S et al. (2020) The accelerator-based boron neutron capture reaction evaluation system for head and neck cancer. Applied Radiation and Isotopes 165, 109271.CrossRefGoogle ScholarPubMed
Zavjalov, E et al. (2020) Accelerator-based boron neutron capture therapy for malignant glioma: a pilot neutron irradiation study using boron phenylalanine, sodium borocaptate and liposomal borocaptate with a heterotopic U87 glioblastoma model in SCID mice. International Journal of Radiation Biology 96, 868–878.CrossRefGoogle ScholarPubMed
Kawabata, S et al. (2021) Accelerator-based BNCT for patients with recurrent glioblastoma: a multicenter phase II study. Neuro-Oncology Advances 3, vdab067.CrossRefGoogle ScholarPubMed
Fukunaga, H et al. (2020) Implications of radiation microdosimetry for accelerator-based boron neutron capture therapy: a radiobiological perspective. The British Journal of Radiology 93, 20200311.CrossRefGoogle ScholarPubMed
Cirrone, G et al. (2018) First experimental proof of proton boron capture therapy (PBCT) to enhance protontherapy effectiveness. Scientific Reports 8, 1141.CrossRefGoogle ScholarPubMed
Hideghéty, K et al. (2019) 11Boron delivery agents for boron proton-capture enhanced proton therapy. Anticancer Research 39, 2265–2276.CrossRefGoogle ScholarPubMed