The Latest in Boron Neutron Capture Therapy Radiobiology

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Radiobiology and Nuclear Medicine".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 10596

Special Issue Editors


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Guest Editor
1. Department of Radiobiology, National Atomic Energy Commission (CNEA), General Paz 1499, San Martín, Buenos Aires B1650KNA, Argentina
2. National Research Council (CONICET), Buenos Aires, Argentina
Interests: radiobiology; boron neutron capture therapy; BNCT; oral cancer; oral precancer; mucositis; microbiota; clinical-veterinary BNCT studies

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Guest Editor
1. Department of Physics, University of Pavia, Pavia, Italy
2. National Institute of Nuclear Physics, Pavia, Italy
Interests: boron neutron capture therapy; dosimetry; treatment planning simulation; BNCT radiobiology and preclinical studies
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Head Radiation Pathology Division, Department of Radiobiology, National Atomic Energy Commission (CNEA), General Paz 1499, San Martín, Provincia de Buenos Aires B1650KNA, Argentina
2. Principal Investigator of the National Research Council of Argentina (CONICET), Buenos Aires, Argentina
Interests: boron neutron capture therapy (BNCT) radiobiology; particle therapy; translational in vivo BNCT studies; clinical veterinary BNCT studies; interdisciplinary national and international collaborations
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is the first or second most common cause of death. Unfortunately, in the next 50 years, the global number of cancer patients is expected to rise. In this sense, there is a need for more effective and selective therapies. Boron neutron capture therapy (BNCT) is a very promising tumor-selective particle radiotherapy. It involves the preferential accumulation of boron carriers in tumor cells, followed by irradiation with a thermal or epithermal neutron beam. Overall BNCT clinical results to date show therapeutic efficacy, associated with an improvement in patient quality of life and prolonged survival. Radiobiological BNCT studies have been of utmost importance to make progress in BNCT, which are also essential to design novel, safe, and effective clinical BNCT protocols (https://isnct.net/).

The aim of this Special Issue is to collect the latest BNCT radiobiological findings performed in in vivo and in vitro experimental models. We also encourage the authors to submit their latest results in the BNCT clinical veterinary field. Contributions should be related to, but not limited to, the study of BNCT for different pathologies, BNCT combined with other cancer therapies, findings related to the radiobiological mechanisms induced by BNCT, the evaluation of new boron compounds, and strategies that could enhance BNCT therapeutic effect and reduce toxicity. We encourage authors to contribute radiobiological findings in the more recently developed area of accelerator based-BNCT, but of course also welcome contributions in the well-established area of reactor-based BNCT.    

Looking forward to receiving many valuable contributions.

Dr. Andrea Monti Hughes
Dr. Silva Bortolussi
Dr. Amanda Schwint
Guest Editors

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Keywords

  • boron neutron capture therapy
  • particle therapy
  • radiobiology
  • experimental studies
  • clinical veterinary studies

Published Papers (5 papers)

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Research

21 pages, 47637 KiB  
Article
Enhanced Resolution of Neutron Autoradiography with UV-C Sensitization to Study Boron Microdistribution in Animal Models
by Agustina Mariana Portu, María Sol Espain, Silvia Inés Thorp, Verónica Andrea Trivillin, Paula Curotto, Andrea Monti Hughes, Emiliano César Cayetano Pozzi, Marcela Alejandra Garabalino, Mónica Alejandra Palmieri, Pablo Nicolás Granell, Federico Golmar, Amanda Elena Schwint and Gisela Saint Martin
Life 2023, 13(7), 1578; https://doi.org/10.3390/life13071578 - 18 Jul 2023
Cited by 1 | Viewed by 998
Abstract
The assessment of boron microdistribution is essential to evaluate the suitability of boron neutron capture therapy (BNCT) in different biological models. In our laboratory, we have reported a methodology to produce cell imprints on polycarbonate through UV-C sensitization. The aim of this work [...] Read more.
The assessment of boron microdistribution is essential to evaluate the suitability of boron neutron capture therapy (BNCT) in different biological models. In our laboratory, we have reported a methodology to produce cell imprints on polycarbonate through UV-C sensitization. The aim of this work is to extend the technique to tissue samples in order to enhance spatial resolution. As tissue structure largely differs from cultured cells, several aspects must be considered. We studied the influence of the parameters involved in the imprint and nuclear track formation, such as neutron fluence, different NTDs, etching and UV-C exposure times, tissue absorbance, thickness, and staining, among others. Samples from different biological models of interest for BNCT were used, exhibiting homogeneous and heterogeneous histology and boron microdistribution. The optimal conditions will depend on the animal model under study and the resolution requirements. Both the imprint sharpness and the fading effect depend on tissue thickness. While 6 h of UV-C was necessary to yield an imprint in CR-39, only 5 min was enough to observe clear imprints on Lexan. The information related to microdistribution of boron obtained with neutron autoradiography is of great relevance when assessing new boron compounds and administration protocols and also contributes to the study of the radiobiology of BNCT. Full article
(This article belongs to the Special Issue The Latest in Boron Neutron Capture Therapy Radiobiology)
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15 pages, 6952 KiB  
Article
NeuTHOR Station—A Novel Integrated Platform for Monitoring BNCT Clinical Treatment, Animal and Cell Irradiation Study at THOR
by Yu-Shiang Huang, Jinn-Jer Peir, Chuan-Jen Wu, Mei-Ya Wang, Yi-Wei Chen, Jia-Cheng Lee and Fong-In Chou
Life 2023, 13(3), 800; https://doi.org/10.3390/life13030800 - 15 Mar 2023
Cited by 3 | Viewed by 1468
Abstract
(1) Background: A well-established Boron Neutron Capture Therapy (BNCT) facility includes many essential systems, which are the epithermal neutron beam system, on-line monitoring system (OMS), QA/QC (quality assurance or quality control) system, boron concentration (BC) measurement system, and treatment planning system (TPS). Accurate [...] Read more.
(1) Background: A well-established Boron Neutron Capture Therapy (BNCT) facility includes many essential systems, which are the epithermal neutron beam system, on-line monitoring system (OMS), QA/QC (quality assurance or quality control) system, boron concentration (BC) measurement system, and treatment planning system (TPS). Accurate data transmission, monitoring, and deposition among these systems are of vital importance before, during, and after clinical, animal, and cell BNCT irradiation. This work developed a novel integrated platform NeuTHOR Station (NeuTHORS) for BNCT at Tsing Hua Open-pool Reactor (THOR). Apart from the data of the OMS and QA/QC system, the data of BC and TPS can be loaded on NeuTHORS before BNCT clinical, animal, and cell irradiation. (2) Methods: A multi-paradigm computer programming language c# (c sharp) was used to develop the integrated platform NeuTHORS. The design of NeuTHORS is based on the standard procedures of BNCT treatment or experiment at THOR. Moreover, parallel testing with OMS-BNCT (the former OMS) and QA/QC of THOR was also performed for more than 70 times to verify the validation of NeuTHORS. (3) Results: According to the comparisons of the output, NeuTHORS and OMS-BNCT and QA/QC of THOR show very good consistency. NeuTHORS is now installed on an industrial PC (IPC) and successfully performs the monitoring of BNCT Treatment at THOR. Patients’ f BC and TPS data are also input into NeuTHORS and stored on IPC through an internal network from BC measurement room and TPS physicist. Therefore, the treatment data of each patient can be instantaneously established after each BNCT treatment for further study on BNCT. NeuTHORS can also be applied on data acquisition for a BNCT-related study, especially for animal or cell irradiation experiments. (4) Conclusions: A novel integrated platform NeuTHOR Station for monitoring BNCT clinical treatment and animal and cell irradiation study has been successfully established at THOR. With this platform, BNCT radiobiology investigations will be efficiently performed and a thorough data storage and analysis system of BNCT treatments or experiments can thus be systematically built up for the further investigation of BNCT at THOR. Full article
(This article belongs to the Special Issue The Latest in Boron Neutron Capture Therapy Radiobiology)
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17 pages, 9780 KiB  
Article
Study of Lithium Biodistribution and Nephrotoxicity in Skin Melanoma Mice Model: The First Step towards Implementing Lithium Neutron Capture Therapy
by Iuliia Taskaeva, Anna Kasatova, Dmitry Surodin, Nataliya Bgatova and Sergey Taskaev
Life 2023, 13(2), 518; https://doi.org/10.3390/life13020518 - 14 Feb 2023
Cited by 3 | Viewed by 1792
Abstract
Boron neutron capture therapy (BNCT) is one of the promising treatment methods for malignant melanoma. The main issue of this technology is the insufficient selectivity of 10B accumulation in tumor cells. As a result of the neutron absorption by boron, an 84% [...] Read more.
Boron neutron capture therapy (BNCT) is one of the promising treatment methods for malignant melanoma. The main issue of this technology is the insufficient selectivity of 10B accumulation in tumor cells. As a result of the neutron absorption by boron, an 84% energy release occurred within the cell by the nuclear reaction 10B (n, α)7Li, which lead to tumor cell death. The use of lithium instead of boron brings a new unique opportunity—local 100% energy release—since all products of the 6Li (n, α)3H reaction have high linear energy transfer characteristics. The aim of this study was to determine the concentrations of Li in the tumor, skin, blood, brain and kidney in experimental animals with B16 melanoma and to analyze the potential Li toxicity after lithium carbonate administration at single doses of 300 and 400 mg/kg. Lithium carbonate was chosen since there is a long-term experience of its use in clinical practice for the treatment of psychiatric disorders. The inductively coupled plasma atomic emission spectrometry was used to evaluate Li concentrations in tissue samples. The accumulation efficiency of Li in the tumor was the highest at a time point of 30 min (22.4 µg/g; at a dose of 400 mg/kg). Despite the high lithium accumulation in the kidneys, the pathological changes in kidney tissues were not found. Thus, lithium may actually be used for the Li-NCT development and future studies can be conducted using 6Li and following irradiation of tumor cells using the schemes of lithium administration tested in this work. Full article
(This article belongs to the Special Issue The Latest in Boron Neutron Capture Therapy Radiobiology)
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13 pages, 3380 KiB  
Article
Therapeutic Efficacy and Radiobiological Effects of Boric-Acid-Mediated BNCT in an Osteosarcoma-Bearing SD Rat Model
by Chen-Fang Hsu, Hong-Ming Liu, Jinn-Jer Peir, Jiunn-Wang Liao, Kuan-Sheng Chen, Yi-Wei Chen, Yung-Jen Chuang and Fong-In Chou
Life 2023, 13(2), 514; https://doi.org/10.3390/life13020514 - 13 Feb 2023
Cited by 3 | Viewed by 1643
Abstract
Background: Osteosarcoma (OS) is the most common primary malignancy of the bone and is notoriously resistant to radiation therapy. High-dose cytotoxic chemotherapy and surgical resection have improved the survival rate and prognosis of patients with OS. Nonetheless, treatment challenges remain when the tumor [...] Read more.
Background: Osteosarcoma (OS) is the most common primary malignancy of the bone and is notoriously resistant to radiation therapy. High-dose cytotoxic chemotherapy and surgical resection have improved the survival rate and prognosis of patients with OS. Nonetheless, treatment challenges remain when the tumor cannot be removed by surgery. Boron neutron capture therapy (BNCT) provides high linear energy transfer (LET) radiation, and its internal targeted characteristics make BNCT a novel therapy for removing OS and reducing radiation damage to adjacent healthy tissues. Methods: In this study, a UMR-106-grafted OS rat model was developed, and boric acid (BA) was used as the boron drug for BNCT. The pharmacokinetics of BA, following intravenous injection, were evaluated to determine the optimal time window for neutron irradiation. OS-bearing rats were irradiated by an epithermal neutron beam at Tsing Hua Open-Pool Reactor (THOR). The therapeutic efficacy of and tissue response after BNCT were evaluated by radiographic and histopathological observations. Results: OS-bearing rats were irradiated by neutrons in the first hour following the intravenous injection of BA. The prescription-absorbed doses in the tumor regions were 5.8 and 11.0 Gy. BNCT reduced the body weight of the tumor-bearing rats, but they recovered after a few days. The BA-mediated BNCT effectively controlled the orthotopic OS tumor, reduced osteolysis, and induced bone healing. Autoradiography and histological analysis confirmed that the BA retention region is consistent with the calcification region in OS tissue. Conclusion: BA is specifically retained in OS, and the BA-mediated BNCT can significantly reduce the tumor burden and osteolysis in OS-bearing rats. Full article
(This article belongs to the Special Issue The Latest in Boron Neutron Capture Therapy Radiobiology)
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13 pages, 2829 KiB  
Article
The Anti-Tumor Effect of Boron Neutron Capture Therapy in Glioblastoma Subcutaneous Xenograft Model Using the Proton Linear Accelerator-Based BNCT System in Korea
by Il Hyeok Seo, Jeongwoo Lee, Dasom Na, Hyunhye Kyung, Jieun Yang, Sangbong Lee, Sang June Jeon, Jae Won Choi, Kyu Young Lee, Jungyu Yi, Jaehwan Han, Mooyoung Yoo and Se Hyun Kim
Life 2022, 12(8), 1264; https://doi.org/10.3390/life12081264 - 19 Aug 2022
Cited by 3 | Viewed by 2785
Abstract
Boron neutron capture therapy (BNCT) is a radiation therapy that selectively kills cancer cells and is being actively researched and developed around the world. In Korea, development of the proton linear accelerator-based BNCT system has completed development, and its anti-cancer effect in the [...] Read more.
Boron neutron capture therapy (BNCT) is a radiation therapy that selectively kills cancer cells and is being actively researched and developed around the world. In Korea, development of the proton linear accelerator-based BNCT system has completed development, and its anti-cancer effect in the U-87 MG subcutaneous xenograft model has been evaluated. To evaluate the efficacy of BNCT, we measured 10B-enriched boronophenylalanine (BPA) uptake in U-87 MG, FaDu, and SAS cells and evaluated cell viability by clonogenic assays. In addition, the boron concentration in the tumor, blood, and skin on the U-87 MG xenograft model was measured, and the tumor volume was measured for 4 weeks after BNCT. In vitro, the intracellular boron concentration was highest in the order of SAS, FaDu, and U-87 MG, and cell survival fractions decreased depending on the BPA treatment concentration and neutron irradiation dose. In vivo, the tumor volume was significantly decreased in the BNCT group compared to the control group. This study confirmed the anti-cancer effect of BNCT in the U-87 MG subcutaneous xenograft model. It is expected that the proton linear accelerator-based BNCT system developed in Korea will be a new option for radiation therapy for cancer treatment. Full article
(This article belongs to the Special Issue The Latest in Boron Neutron Capture Therapy Radiobiology)
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