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2018, Scientific Reports
Protontherapy is hadrontherapy’s fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy’s superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular leth...
Applied Sciences, 2021
Protontherapy (PT) is a fast-growing cancer therapy modality thanks to much-improved normal tissue sparing granted by the charged particles’ inverted dose-depth profile. Protons, however, exhibit a low biological effectiveness at clinically relevant energies. To enhance PT efficacy and counteract cancer radioresistance, Proton–Boron Capture Therapy (PBCT) was recently proposed. PBCT exploits the highly DNA-damaging α-particles generated by the p + 11B→3α (pB) nuclear reaction, whose cross-section peaks for proton energies of 675 keV. Although a significant enhancement of proton biological effectiveness by PBCT has been demonstrated for high-energy proton beams, validation of the PBCT rationale using monochromatic proton beams having energy close to the reaction cross-section maximum is still lacking. To this end, we implemented a novel setup for radiobiology experiments at a 3-MV tandem accelerator; using a scattering chamber equipped with an Au foil scatterer for beam diffusion on ...
RAD Conference Proceedings, 2020
Proton therapy is used today to treat many cancers and is particularly appropriate in situations where surgery options are limited, and conventional radiotherapy presents unacceptable risks to patients. A few years ago, it was suggested that an increase of up to a factor of two of the doses at the proton Bragg peak could be achieved if boron is accumulated in the tumor tissues. The mechanism responsible for a higher dose was suggested to be related to proton-boron fusion reactions, leading to the production of high Linear Energy Transfer (LET) α-particles. Nowadays there are single works showing the effectiveness of proton beam irradiation boron-11-containing cancer cells. A limited number of the studies devoted to the application of 11B(p,3a) nuclear reaction in proton therapy and lack of consistency in their results do not allow to judge about the prospects of the boron-containing drugs utilization in proton therapy to increase its antitumor efficacy. In this work, we experimentally test the possibility to enhance proton biological effectiveness in boron-11-containing cancer cells in vitro. Human glioblastoma cells were preincubated with boron compound (Na2B4O7, sodium tetraborate) and irradiated with increasing doses 2-8 Gy at the proton Bragg peak. To test whether the physical nuclear reaction 11B(p,3a) results in an enhancement of the cancer cell death by high-energy proton beam irradiation, cell lines were also irradiated with graded doses 2-8 Gy using γ-ray source. The ability of boron compound to activate the cancer cell death with protons at the Bragg peak irradiation was shown in vitro. At the same time, weaker similar effect was determined for gamma-irradiation that may indicate not only the physical nature of influence boron at irradiated cancer cell viability but a specific biological effect. The data suggest that the combined effect of proton therapy with 11 B on glioma cells increases their sensitivity to proton irradiation with low toxicity of the boron compound for cells of normal morphology.
2021
increased both frequency and complexity of CAs in MCF-10A cells at the mid-and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.
Biomedical Journal of Scientific and Technical Research, 2019
Radiation therapy plays an important role in standard cancer treatment. However, patients who are resistant to traditional radiation therapy or who have relapsed after conventional radiation therapy are often encountered in clinical practice. There is therefore a need for a new radiation therapy for this type of patient. Although boron neutron capture therapy is not a new concept of radiation therapy, due to technological breakthroughs and conceptual improvements at the start of the 21 st century, this therapy, which covers multidisciplinary technologies, such as medical physics, atomic science and technology, boron-containing drug synthesis, radiobiology, and clinical oncology has advanced greatly, and has gradually matured to a clinically useful therapy for patients with cancer. This article provides a brief introduction to the latest breakthroughs and progress in this technology.
Scientific Reports, 2023
Proton boron capture therapy (PBCT) has emerged from particle acceleration research for enhancing the biological effectiveness of proton therapy. The mechanism responsible for the dose increase was supposed to be related to proton-boron fusion reactions (11 B + p → 3α + 8.7 MeV). There has been some experimental evidence that the biological efficiency of protons is significantly higher for boron-11-containing prostate or breast cancer cells. The aim of this study was to evaluate the sensitizing potential of sodium borocaptate (BSH) under proton irradiation at the Bragg peak of cultured glioma cells. To address this problem, cells of two glioma lines were preincubated with 80 or 160 ppm boron-11, irradiated both at the middle of 200 MeV beam Spread-Out Bragg Peak (SOBP) and at the distal end of the 89.7 MeV beam SOBP and assessed for the viability, as well as their ability to form colonies. Our results clearly show that BSH provides for only a slight, if any, enhancement of the effect of proton radiation on the glioma cells in vitro. In addition, we repeated the experiments using the Du145 prostate cancer cell line, for which an increase in the biological efficiency of proton irradiation in the presence of sodium borocaptate was demonstrated previously. The data presented add new argument against the efficiency of proton boron capture therapy when based solely on direct doseenhancement effect by the proton capture nuclear reaction, underlining the need to investigate the indirect effects of the secondary alpha irradiation depending on the state and treatment conditions of the irradiated tissue. Proton therapy (PT) has been applied for many years for the treatment of patients with different types of cancer. PT is characterized by a well-defined dose deposition in tissue with a sharp increase of the absorbed dose at a specific depth which depends on the initial beam energy (Bragg Peak) 1. Beyond the Bragg Peak region, where the major part of the beam energy is absorbed, the dose drops sharply within next few millimeters of tissue. Such a dose distribution makes it possible to achieve a higher absorbed dose in the tumor region keeping the radiation damage to the surrounding tissue at acceptable level. Proton therapy could be particularly appropriate for the treatment of brain tumors, as it allows for the precise delivery of the radiation to the specific region of brain 2. Gliomas are the most common primary brain tumors with an incidence rate of about 6 cases per 100,000 population per year 3. The median survival of patients with low-grade glioma can range from 6 to more than 15 years 3 , whereas the median survival for patients with glioblastoma, the most frequent and malignant highgrade gliomas, is often reported as few months 3-5. The dosimetric advantages and the safety of PT for treatment of gliomas have been previously reported 6,7. Several tumor-specific drugs are under development to improve the overall effectiveness of currently employed radio therapy, including PT, towards high-grade gliomas 8,9 , underlining the overall interest in targeted therapies aimed at improving the therapeutic ratio by increasing the selectivity of radio therapy toward the tumor cells and thus decreasing its adverse effects on the normal tissues 9. One of the emerging treatment modalities designed to improve the therapeutic ratio is boron neutron capture therapy (BNCT) which is based on neutron capture by non-radioactive 10 B nuclei, a nuclear reaction process
Cornell University - arXiv, 2017
Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12 C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12 C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11 Bà3a reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10 B-enriched BSH for neutron irradiation-triggered alpha-particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12 C-ion therapy is thus demonstrated.
Anticancer Research, 2019
The aim of this review was to define appropriate 11 B delivery agents for boron proton-capture enhanced proton therapy (BPCEPT) taking into account the accumulated knowledge on boron compounds used for boron neutron capture therapy (BNCT). BPCEPT is a promising treatment approach which uses a high linear energy transfer (LET) dose component in conjunction with conventional proton therapy to increase the relative biological effectiveness of highly-selective charged particle therapy. Boron proton fusion reactions occur with highest cross section at certain proton energy level and thus can be tailored to the target volume with careful treatment planning that defines the 675 MeV proton distribution with high accuracy. Appropriate 11 B compounds are required in order to achieve relevant high LET dose contribution from the boron proton-capture reaction. Previous scientific results and experiences with BNCT provide background knowledge and information regarding the optimization of boronated compound development, their characterization, measurement and imaging. However, there are substantial differences between BNCT and BPCEPT, which in turn places special unique chemical, physical and biological demands on 11 B-carrier compounds for BPCEPT. In this review, we evaluate well-known and recently developed boron compounds for BPCEPT.
Technology in cancer research & treatment, 2003
Boron neutron capture therapy (BNCT) is based on the preferential targeting of tumor cells with (10)B and subsequent activation with thermal neutrons to produce a highly localized radiation. In theory, it is possible to selectively irradiate a tumor and the associated infiltrating tumor cells with large single doses of high-LET radiation while sparing the adjacent normal tissues. The mixture of high- and low-LET dose components created in tissue during neutron irradiation complicates the radiobiology of BNCT. Much of the complexity has been unravelled through a combination of preclinical experimentation and clinical dose escalation experience. Over 350 patients have been treated in a number of different facilities worldwide. The accumulated clinical experience has demonstrated that BNCT can be delivered safely but is still defining the limits of normal brain tolerance. Several independent BNCT clinical protocols have demonstrated that BNCT can produce median survivals in patients wi...
IntechOpen eBooks, 2023
The lightest ions beyond protons, principally helium, lithium, and boron ions, make highly specific molecular Bragg peak radiation therapy of malignant tumors possible with minimal adverse normal tissue reactions. The Bragg peak ionization density is mainly elevated in a few mm wide spot at the end of these ions with substantially increased local apoptosis and senescence induction. Mainly placing Bragg peaks in the gross tumor volume with increased local therapeutic effect and only low ionization density and easily repairable damage in normal tissues. The possible geometrical accuracy of the dose delivery will be ≈1 mm with these ions. Interestingly, high-resolution molecular tumor imaging will then be possible, particularly with 8 Boron ions that are our lightest positron emitter allowing immediate accurate PET-CT imaging to delineate the target volume dose delivery. Compared to carbon ions the boron radiation damage to normal tissues in front of and behind the tumor is reduced at the same time as tumor apoptosis and senescence are increased. A mean tumor cure as high as 80% should be possible with Boron ion therapy using new clinical fractionation principles and even more when early tumor detection and malignancy estimation methods are brought into more regular clinical use.
Cancer is the biggest question-mark for the medical science. However many effective drugs are available for the cancer treatment, the biggest obstacle is the selective targeting the drug to the cancer cells. Boron Neutron Capture Therapy(BNCT) is a selective therapy of the cancer, it may not affect or affect little to the normal cells, It works on 2 principles - (1)Boron can capture the neutron & getting unstable. (2) Subsequently nuclear fission of boron occurs via emitting radiation. So, Delivered the required dose of boron to the cancerous cells and triggering it with the Neutron beam to this cancer cells which contain the boron, This neutron is capture by the neutron of cancer cells, getting unstable & subsequently nuclear fission is occur, this lethal radiation ultimately kills the cancer cells & normal cells are survive. The nuclear reaction is: 10B + nth → [11B] → α + 7Li + 2.31 MeV The future prospective are to limit the radiation to the cancer cells only & efficiently deliver the Boron to the cancer cell only, also evaluate the other radioactive materials like Gadolinium in place of Boron.
Scientific Reports
The present work introduced a framework to investigate the effectiveness of proton boron fusion therapy (PBFT) at the cellular level. The framework consisted of a cell array generator program coupled with PHITS Monte Carlo package with a dedicated terminal-based code editor that was developed in this work. The framework enabled users to model large cell arrays with normal, all boron, and random boron filled cytoplasm, to investigate the underlying mechanism of PBFT. It was found that alpha particles and neutrons could be produced in absence of boron mainly because of nuclear reaction induced by proton interaction with 16O, 12C and 14N nuclei. The effectiveness of PBFT is highly dependent on the incident proton energy, source size, cell array size, buffer medium thickness layer, concentration and distribution of boron in the cell array. To quantitatively assess the effectiveness of PBFT, of the total energy deposition by alpha particle for different cases were determined. The number ...
BNCT is a tumour treatment based on thermal-neutron irradiation of tissues enriched with 10 B, which according to the 10 B(n, ) 7 Li reaction produces particles with high Linear Energy Transfer and short range. Since this treatment can deliver a therapeutic tumour dose sparing normal tissues, BNCT represents an alternative for diffuse tumours and metastases, which show poor response to surgery and photontherapy. In 2001 and 2003, in Pavia BNCT was applied to an isolated liver, which was infused with boron, explanted, irradiated and re-implanted. A new project was then initiated for lung tumours, developing a protocol for Boron concentration measurements and performing organ-dose Monte Carlo calculations; in parallel, radiobiology studies are ongoing to characterize the BNCT effects down to cellular level. After a brief introduction, herein we will present the main activities ongoing in Pavia including the radiobiological ones, which are under investigation not only experimentally but also theoretically, basing on a Monte Carlo code recently extended to simulate cell killing.
International Journal of Particle Therapy
Mechanism of Action External beam, whether with photons or particles, remains as the most common type of radiation therapy. The main drawback is that radiation deposits dose in healthy tissue before reaching its target. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when 10B is irradiated with low-energy (0.0025 eV) thermal neutrons. The resulting 10B(n,α)7Li capture reaction produces high linear energy transfer (LET) α particles, helium nuclei (4He), and recoiling lithium-7 (7Li) atoms. The short range (5-9 μm) of the α particles limits the destructive effects within the boron-containing cells. In theory, BNCT can selectively destroy malignant cells while sparing adjacent normal tissue at the cellular levels by delivering a single fraction of radiation with high LET particles. History BNCT has been around for many decades. Early studies were promising for patients with malignant brain tumors, recurrent tumors of the head and ne...
Arquivos Brasileiros de Endocrinologia & Metabologia, 2007
Undifferentiated thyroid cancer (UTC) is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron non-radioactive compounds by a tumor, and the subsequent irradiation of the area with an appropriate neutron beam. 10B is then activated to 11B, which will immediately decay releasing alpha particles and 7Li, of high linear energy transfer (LET) and limited reach. Clinical trials are being performed in patients with glioblastoma multiforme and melanoma. We have explored its possible application to UTC. Our results demonstrated that a cell line of human UTC has a selective uptake of borophenylalanine (BPA) both in vitro and after transplantation to nude mice. Treatment of mice by BNCT led to a complete control of gr...
International Journal of Radiation Oncology*Biology*Physics, 1994
Purpose: For many years neutron radiation has been used to treat malignant disease both as fast neutron radiotherapy and as thermal neutron induced boron neutron capture therapy (BNCT). To date, these two approaches have been used independently of one another due to the large difference in neutron energies each employs. In this paper we discuss the potential application of BNCT to enhance the therapeutic effectiveness of a fast neutron radiotherapy beam. Methods and Materials: Measurements are presented for the thermal neutron component that is spontaneously developed as the University of Washington fast neutron radiotherapy beam penetrates a water phantom. The biological effect of this thermalized component on cells "tagged" with boron-10 ("B) is modeled mathematically and the expected change in cell survival calculated. The model is then extended to estimate the effect this enhanced cell killing would have for increased tumor control. Results: The basic predictions of the model on changes in cell survival are verified with in vitro measurements-the V-79 cell line. An additional factor of lo-100 in tumor cell killing appears achievable with currently available l"B carriers using our present neutron beam. A Poisson model is then used to estimate the change in tumor control this enhanced cell killing would produce in various clinical situations and the effect is sufficiently large so as to be clinically relevant. It is also demonstrated that the magnitude of the thermalized component can be increased by a factor of 2-3 with relatively simple changes in the beam generating conditions. Conclusion: BNCI may provide a means of enhancing the therapeutic effectiveness of fast neutron radiothearapy in a wide variety of clinical situations and is an area of research that should be aggressively pursued. Fast neutron radiotherapy, BNCT, Neutron capture, Boron.
2015
Since the response at conventional chemoand radio therapy treatment of hepatocellular carcinoma is extremely reduced, the research of the specialists from this domain were oriented to find new alternative therapies to assur e a better response to the treatment of primary or metastatic liver tumors. The neutron cap ture by Boron-10 radiotherapy is a therapeutic method being in the pioneer’s work stag e especially in Europe, but with promising results, especially in brain tumor so far . The Boron neutrons capture are producing alpha energetic particles, with a high li near energetic transfer at tissue level. Consequently it obtains higher cell destruction and greater biological relative efficiency than in the case of photons. Using adequate Boron co mpounds, preferentially localized in tumor cells and not in the healthy tissue, the Bo ron neutrons capture therapy gives a higher curative potential with lower toxicity in no rmal tissues. The aim of our study is to establish one in vivo ...
Radiation Oncology, 2021
Boron neutron capture therapy (BNCT) was first proposed as early as 1936, and research on BNCT has progressed relatively slowly but steadily. BNCT is a potentially useful tool for cancer treatment that selectively damages cancer cells while sparing normal tissue. BNCT is based on the nuclear reaction that occurs when 10B capture low-energy thermal neutrons to yield high-linear energy transfer (LET) α particles and recoiling 7Li nuclei. A large number of 10B atoms have to be localized within the tumor cells for BNCT to be effective, and an adequate number of thermal neutrons need to be absorbed by the 10B atoms to generate lethal 10B (n, α)7Li reactions. Effective boron neutron capture therapy cannot be achieved without appropriate boron carriers. Improvement in boron delivery and the development of the best dosing paradigms for both boronophenylalanine (BPA) and sodium borocaptate (BSH) are of major importance, yet these still have not been optimized. Here, we present a review of th...
JURNAL TEKNOLOGI REAKTOR NUKLIR TRI DASA MEGA, 2021
Liver cancer was the third leading cause of death from cancer in 2020 with 830,180 deaths worldwide. Radiotherapy is a common treatment method for liver cancer. Technological advances presented proton therapy and boron neutron capture therapy (BNCT) as alternatives with a lower dose on healthy organs. The objective of this research is to get a good dose distribution with higher tumor dose and lower healthy organ dose in proton therapy. A comparison with BNCT is done to get a better understanding of how both methods deliver the dose to treat the cancer while minimizing healthy organ doses. The research simulated proton therapy for cancer liver with Particle and Heavy Ions Transport Code System (PHITS), and a literature review for BNCT. The effectiveness of both methods were compared by tumor dose and liver dose. The optimal tumor dose for proton therapy is 86.01 Gy (W) with 0.67 Gy (W) liver dose. Proton therapy can replace conventional radiotherapy for tumors with complex shapes in ...
International Journal of Radiation Oncology*Biology*Physics, 1993
The purpose of this study was to independently determine RBE values for all of the boron neutron capture therapy dose components.
Applied Radiation and Isotopes, 2009
Binary treatment modality Early clinical trials Radiotherapy Trial design Boron neutron capture therapy (BNCT) BSH BPA a b s t r a c t BNCT causes selective damage to tumor cells by neutron capture reactions releasing high LET-particles where 10 B-atoms are present. Neither the 10 B-compound nor thermal neutrons alone have any therapeutic effect. Therefore, the development of BNCT to a treatment modality needs strategies, which differ from the standard phase I-III clinical trials. An innovative trial design was developed including translational research and a phase I aspect. The trial investigates as surrogate endpoint BSH and BPA uptake in different tumor entities.
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