A recombination chamber-based measurement system for radiation protection in neutron medical and research centers.

The current radiobiological model employed for boron neutron capture therapy (BNCT) treatment planning, which relies on microdosimetry, fails to provide an accurate representation the biological effects of BNCT. The precision in calculating the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) plays a pivotal role in determining the therapeutic efficacy of BNCT. Therefore, this study focuses on how to improve the accuracy of the biological effects of BNCT. The purpose of this study is to propose new radiation biology models based on nanodosimetry to accurately assess RBE and CBE for BNCT. Nanodosimetry, rooted in ionization cluster size distributions (ICSD), introduces a novel approach to characterize radiation quality by effectively delineating RBE through the ion track structure at the nanoscale. In the context of prior research, this study presents a computational model for the nanoscale assessment of RBE and CBE. We establish a simplified model of DNA chromatin fiber using the Monte Carlo code TOPAS-nBio to evaluate the applicability of ICSD to BNCT and compute nanodosimetric parameters. Our investigation reveals that both homogeneous and heterogeneous nanodosimetric parameters, as well as the corresponding biological model coefficients α and β, along with RBE values, exhibit variations in response to varying intracellular 10B concentrations. Notably, the nanodosimetric parameter effectively captures the fluctuations in model coefficients α and RBE. Our model facilitates a nanoscale analysis of BNCT, enabling predictions of nanodosimetric quantities for secondary ions as well as RBE, CBE, and other essential biological metrics related to the distribution of boron. This contribution significantly enhances the precision of RBE calculations and holds substantial promise for future applications in treatment planning.

Boron Neutron Capture Therapy (BNCT) is an advanced form of radiotherapy technique that is potentially superior to all conventional techniques for cancer treatment, as it is targeted at killing individual cancerous cells with minimal damage to surrounding healthy cells. After decades of development, BNCT has reached clinical-trial stages in several countries, mainly for treating challenging cancers such as malignant brain tumors. The Indonesian consortium of BNCT already developed of the design BNCT for many cases of type cancers using many neutron sources. The main objective of the Indonesian consortium BNCT are the development of BNCT technology package which consists of a non nuclear reactor neutron source based on cyclotron and compact neutron generator technique, advanced boron-carrying pharmaceutical, and user-friendly treatment platform with automatic operation and feedback system as well as commercialization of the BNCT though franchised network of BNCT clinics worldwide. The Indonesian consortium BNCT will offering to participate in Boron carrier pharmaceuticals development and testing, development of cyclotron and compact neutron generators and provision of neutrons from the 100 kW Kartini Research Reactor to guide and to validate compact neutron generator development. Studies were carried out to design a collimator which results in epithermal neutron beam for Boron Neutron Capture Therapy (BNCT) at the Kartini Research Reactor by means of Monte Carlo N-Particle 5 (MCNP5) codes. Reactor within 100 kW of output thermal power was used as the neutron source. The design criteria were based on the IAEA’s recommendation. All materials used were varied in size, according to the value of mean free path for each. Monte Carlo simulations indicated that by using 5 cm thick of Ni as collimator wall, 60 cm thick of Al as moderator, 15 cm thick of 60Ni as filter, 1,5 cm thick of Bi as "-ray shielding, 3 cm thick of 6Li2CO3-polyethylene as beam delimiter, with 3-5 cm varied aperture size, epithermal neutron beam with minimum flux of 7,8 x 108 n.cm-2.s-1, maximum fast neutron and "-ray components of, respectively, 1,9 x 10-13 Gy.cm2.n-1 and 1,8 x 10-13 Gy.cm2.n-1, maximum thermal neutron per epithermal neutron ratio of 0,009, and beam minimum directionality of 0,72, could be produced. The beam did not fully pass the IAEA’s criteria, since the epithermal neutron flux was still below the recommended value, 1,0 x 109 n.cm-2.s-1. Nonetheless, it was still usable with epithermal neutron flux exceeded 5 x 108 n.cm-2.s-1. When this collimator was surrounded by 8 cm thick of graphite, the characteristics of the beam became better that it passed all IAEA’s criteria with epithermal neutron flux up to 1,7 x 109 n.cm-2.s-1. it is still feasible for BNCT in vivo experiment and study of many cases cancer type i.e.; liver and lung curcinoma. In this case, thermal neutron produced by model of Collimated Thermal Column Kartini Research Nuclear Reactor, Yogyakarta. Sodium boroncaptate (BSH) was used as in this research. BSH had effected in liver for radiation quality factor as 0.8 in health tissue and 2.5 in cancer tissue. Modelling organ and source used liver organ who contain of cancer tissue and research reactor. Variation of boron concentration was 20, 25, 30, 35, 40, 45, and 47 $g/g cancer. Output of MCNP calculation were neutron scattering dose, gamma ray dose and neutron flux from reactor. Given the advantages of low density owned by lungs, hence BNCT is a solid option that can be utilized to eradicate the cell cancer in lungs. Modelling organ and neutron source for lung carcinoma was used Compact Neutron Generator (CNG) by deuterium-tritium which was used is boronophenylalanine (BPA). The concentration of boron-10 compound was varied in the study; i.e. the variations were 20; 25; 30; 35; 40 and 45 μg.g-1 cancer tissues. Ideally, the primary dose which is solemnly expected to contribute in the therapy is alpha dose, but the secondary dose; i.e. neutron scattering dose, proton dose and gamma dose that are caused due to the interaction of thermal neutron with the spectra of tissue can not be simply omitted. Thus, the desired output of MCNPX; i.e. tally, were thermal and epithermal neutron flux, neutron and photon dose. The liver study variation of boron concentration result dose rate to every variation were0,042; 0,050; 0,058; 0,067; 0,074; 0,082; 0,085 Gy/sec. Irradiation time who need to every concentration were 1194,687 sec (19 min 54 sec);999,645 sec (16 min 39 sec); 858,746 sec (14 min 19 sec); 743,810 sec (12 min 24 sec); 675,156 sec (11 min 15 sec); 608,480 sec (10 min 8 sec); 585,807sec (9 min 45 sec). The lung carcinoma study variations of boron-10 concentration in tissue resulted in the dose rate of each variables respectively were 0.003145, 0.003657, 0.00359, 0.00385, 0.00438 and 0.00476 Gy.sec-1 . The irradiated time needed for therapy for each variables respectively were 375.34, 357.55, 287.58, 284.95, 237.84 and 219.84 minutes.

<p indent=0mm>Boron neutron capture therapy (BNCT) is regarded as a revolutionary means for high-accuracy cancer therapy with cell level selectivity. It has unique therapeutic effects for some malignance, such as glioblastoma multiforme, melanoma, recurrent head and neck malignance. It can also be used for cancer treatment of deep organ, such as liver and lung. Even though its principle was proposed about <sc>80 years</sc> ago, it has never been utilized in routine clinic therapy in hospital until 2020. BNCT, as a binary therapeutic method, greatly depends on both high-quality neutron beam and highly target-selective boron drug. Tumor killing in cell-level accuracy can be achieved only when the two elements work together and collaborate closely. To realize such therapeutic effect, BNCT sets high requirement on both neutron source and boron drug. The research on boron drug is related with multi-disciplines, such as chemistry, biology, medicine, radiology, pharmacy and physics. This article focuses on the neutron source for BNCT. Commonly, there are two types of BNCT neutron sources: reactor-based neutron source and accelerator-based neutron source. Up to now, almost all clinic trails of BNCT therapy were performed with the former. Due to limited resources of reactor neutron source, only less than 2000 cases BNCT treatments have been carried out in the world since BNCT method was invented. Thanks for the intense beam proton accelerator development, accelerator based neutron source can provide better beam quality, and especially importantly it can be installed in a hospital environment, which is essential for wide-range application of BNCT. In accelerator-based BNCT field, China has a sound base owing to more than <sc>20 years</sc> research and development in high intensity neutron source for spallation neutron source and accelerator-driven subcritical system. It is meaningful work to transfer the related technology to accelerator-based BNCT (AB-BNCT). In this paper we will firstly introduce the demand on neutron beam specification recommended by IAEA. Then the difficulties in BNCT slow development in passing decades are reviewed. New era of BNCT is coming and one can expect a prosperous future, owing to accelerator-based BNCT. The core technology of AB-BNCT is explored and recent research achievements on BNCT research and development in China are reported. Various types of accelerators now can be used for BNCT facility, including electro-static high voltage, cyclotron and RF linac. Their pro and con are reviewed. Majorly two kinds of neutron generation targets are utilized for BNCT, and the characteristics comparison of these two are analyzed. On the newly constructed BNCT research platform in China, new boron drug research and development work are conducted in many institutes, universities and pharmacy companies. And in recent, a new AB-BNCT facility is under construction for clinic trails in a hospital. So we can have an optimistic viewpoint for BNCT future in China.

During any radiation therapy, the therapeutic tumor dose is limited by the tolerance of the surrounding normal tissue within the treatment volume. The short ranges of the products of the 10B(n,α)7Li reaction produced during boron neutron capture therapy (BNCT) present an opportunity to increase the therapeutic ratio (tumor dose/normal tissue dose) to levels unprecedented in photon radiotherapy. The mixed radiation field produced during BNCT comprises radiations with different linear energy transfer (LET) and different relative biological effectiveness (RBE). The short ranges of the two high-LET products of the 10B(n,α)7Li reaction make the microdistribution of the boron relative to target cell nuclei of particular importance. Due to the tissue specific distribution of different boron compounds, the term RBE is inappropriate in defining the biological effectiveness of the 10B(n,α)7Li reaction. To distinguish these differences from true RBEs we have used the term “compound biological effectiveness” (CBE) factor. The latter can be defined as the product of the true, geometry-independent, RBE for these particles times a “boron localization factor”, which will most likely be different for each particular boron compound. To express the total BNCT dose in a common unit, and to compare BNCT doses with the effects of conventional photon irradiation, multiplicative factors (RBEs and CBEs) are applied to the physical absorbed radiation doses from each high-LET component. The total effective BNCT dose is then expressed as the sum of RBE-corrected physical absorbed doses with the unit Gray-equivalent (Gy-Eq).

A Retrospective Study of Predictors for Radiation Induced Severe Oral Mucositis in BPA-Mediated BNCT of Head and Neck Cancer Patients

The neutron beam in a boron neutron capture therapy (BNCT) irradiation field comprises a range of energies with different relative biological effectiveness. The neutron energy spectrum can change over time due to variations in the neutron source. Current methods for measuring the neutron energy spectrum are impractical and have significant limitations, such as being time-consuming and posing radiation exposure risks; therefore, neutron energy spectrum measurement has not been incorporated into routine BNCT quality assurance (QA) procedures. To address these issues, we developed a cylindrical hemisphere accurate remote multilayer spectrometer (CHARMS) that integrates a liquid moderator supply and drainage system with real-time neutron detection for suitable use in the BNCT QA procedure. To validate CHARMS for QA procedures in BNCT irradiation field. We conducted experimental validations of CHARMS at the Heavy Water Neutron Irradiation Facility of Kyoto University Reactor under two irradiation conditions (with and without a collimator), performing three separate measurement sessions over 3 months. The total measurement time required by CHARMS to achieve a target neutron count uncertainty below 1% was less than 10min. Monitoring the neutron counts at ten uniformly spaced intervals during each measurement showed that most counts fell within a Poisson-derived standard deviation. The neutron energy spectrum under irradiation without collimator was successfully evaluated. However, because of the effects of the neutron beam intensity and angular distribution in BNCT, the neutron energy spectrum under irradiation with collimator could not be properly evaluated. The validity of the CHARMS for QA procedures in BNCT was confirmed. The rapid measurements and stable operation of the liquid moderator injection and drainage system show that CHARMS is well-suited for routine BNCT QA, eliminating the need for moderator replacement and thereby minimizing radiation exposure. Future work will address the challenges related to neutron beam intensity and angular distribution to enable the evaluation of neutron energy spectrum unfolding under collimated irradiation conditions, which is essential for clinical BNCT.

Introduction: Recently head and neck cancer has pay attention to many researchers. Its therapeutic methods include surgery, chemotherapy, radiotherapy and Boron neutron capture therapy (BNCT). BNCT is better than conventional radiotherapy because it targets the tumor cell. This method involves two steps of infusion of stable 10B and then neutron radiation with a suitable intensity and energy. The BNCT in combination with boronphenylalanine (BPA) and borocaptate sodium (BSH) that was make using the epithermal neutron. BSH and PBA are used as 10B carriers. Epithermal neutrons reach to thermal transiting through tissues of the body. When 10B absorbed thermal neutrons, the α and 7Li particles produced in the 10B (n, α) 7Li reaction are of high linear energy. Transfer radiation have a short range of one cell diameter. Materials and Methods: Monte Carlo simulations were performed with MCNPX2.6 and RO31 MIRD phantom. The neutron source was employed the surface disk with 10 diameters and the range of energy was considered from 1ev-10Kev. The results of neutron and gamma dose at various depths was calculated using tally F4 and F6 in MCNPX2.6 code. Results: Relative Dose was obtained at various depths based on energy changes for gamma, fast and thermal neutron. The results of this study have shown increases of optimum energy as the tumor get deeper respect to the skin. In addition, an analytical relation was proposed for energy optimization with the position of the tumor. Conclusion: The optimum neutron energy dependence was investigated for neck tumor in different depths. These results provide useful information to the physicians to choice best optimum energy neutron beam in BNCT method.

Microdosimetry for the characterization of the THOR epithermal neutron beam

Intestinal crypt regeneration in mice : a biological system for quality assurance in non-conventional radiation therapy

Microdosimetry study of THOR BNCT beam using tissue equivalent proportional counter

In Boron Neutron Capture Therapy (BNCT) microdosimetry of charged particle radiation depends on total boron concentration and intracellular boron distribution. Due to the inhomogeneity of boron distribution in cells, radiation doses to both tumor and normal tissue are influenced by boron and nitrogen concentrations and intracellular distributions, cell volume and shape, nuclear size and geometrical structure of the tissue. For correct calculation of the radiation dose in BNCT, these factors should be taken into account. Several computer models have been developed previously in order to estimate the absorbed dose from charged particles in BNCT (Gabel et al. 1987; Kobayashi and Kanda, 1982). In these models, however, single values for mean Relative Biological Effectiveness (RBE) are used to convert high LET radiation doses to isoeffective photon equivalent doses. The RBE depends on both LET and endpoint, such as surviving fraction of tumor cells or normal tissue tolerance (Barendsen et al. 1966). Since LET is not constant along the track of a charged particle, the RBE cannot be considered constant for particles generated by boron and nitrogen neutron capture. Experimental RBE data to be used in BNCT have been gathered, but without consensus (Gabel et al. 1984; Fukuda et al. 1987).

Microdosimetric Modeling of Relative Biological Effectiveness for Skin Reactions: Possible Linkage Between In Vitro and In Vivo Data

Boron neutron capture therapy (BNCT) is a cancer-selective radiotherapy that utilizes the cancer targeting 10B-compound. Cancer cells that take up the compound are substantially damaged by the high liner energy transfer (LET) particles emitted mainly from the 10B(n, α7Li reaction. BNCT can minimize the dose to normal tissues, but it must be performed within the tolerable range of normal tissues. Therefore, it is important to evaluate the response of normal tissues to BNCT. Since BNCT yields a mixture of high and low LET radiations that make it difficult to understand the radiobiological basis of BNCT, it is important to evaluate the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for assessing the responses of normal tissues to BNCT. BSH and BPA are the only 10B-compounds that can be used for clinical BNCT. Their biological behavior and cancer targeting mechanisms are different; therefore, they affect the CBE values differently. In this review, we present the RBE and CBE values of BPA or BSH for normal tissue damage by BNCT irradiation. The skin, brain (spinal cord), mucosa, lung, and liver are included as normal tissues. The CBE values of BPA and BSH for tumor control are also discussed.

<p indent="0mm">Boron neutron capture therapy (BNCT) is an emerging radiotherapeutic modality aimed at selectively concentrating boron compounds in tumor cells and then subjecting the tumor cells to neutron beam radiation. Treatment with BNCT is based on the nuclear capture and fission reactions that occur when nonradioactive boron-10 (¹⁰B) is irradiated with neutrons to yield an alpha particle (helium, ⁴He) and a recoiling lithium-7 (⁷Li) nuclei. The ⁴He particle has a range of <sc>9 μm</sc> and the ⁷Li particle <sc>5 μm</sc> in tissue. In theory, the short range of this reaction limits the damage to malignant cells while sparing adjacent normal cells. The development of BNCT is still constrained by the progress in developing boron delivery agents with a high tumor uptake, low normal tissue uptake, and optimizing the dosing paradigms and quantitative estimation of the ¹⁰B concentrations. It is widely recognized that the second generation boron-containing agents, sodium borocaptate (BSH) and boronophenylalanine (BPA), are less than ideal. New and more effective boron-containing agents are urgently required for clinical use to deliver the requisite amounts of boron to tumor cells. The delivery of boron-containing agent can also be optimized to improve cancer cell uptake and subcellular distribution. Additionally, it is crucial to design high intensity neutron sources and establish hospital-based BNCT. Compared with nuclear reactors, accelerator-based neutron sources are more realistic to be applied in clinical practice. In future, the critical issues regarding novel boron-containing agents, the appropriate delivery strategies, and neutron sources of BNCT for clinical use must be addressed. Two clinical trials with newly diagnosed glioblastoma have been reported, BNCT alone after surgery provided a mean survival time of 17.7 and <sc>19.5 months</sc> respectively. The survival outcomes were good as compared to the current standard of care which is post-operation fractionated radiotherapy with concomitant and adjuvant TMZ. Several clinical studies of BNCT in the treatment of recurrent head and neck cancer have been reported, with high response rate and acceptable toxicity. To date, BNCT has been clinically evaluated as an alternative to conventional radiotherapy for the treatment of several tumor types, including newly diagnosed glioblastoma, recurrent glioma, recurrent head and neck tumors, meningioma, malignant melanoma, and liver metastasis. Recently, accelerator-based neutron source has been used in clinical trials for recurrent malignant gliomas and head &amp; neck cancers. Although initial results with BNCT are promising, high-quality prospective clinical trials are still lacking. Well-designed phase II/III clinical research is necessary to define the efficacy and safety of BNCT in various tumor types. Meanwhile, studies comparing the outcomes of BNCT with other standards of care are needed for the further development of BNCT. Based on the previous studies, the BNCT clinical trials in glioblastoma can be initiated with newly diagnosed glioblastoma patients. For other tumor types, late-stage patients with recurrent or metastatic disease after the first-line treatment might be recruited. Last but not the least, in the era of comprehensive treatment for malignant tumor, it is necessary to explore the combined treatment mode of BNCT. For the future research, BNCT may be coupled with a variety of anti-tumor modalities, including traditional photon radiotherapy, immunotherapy, targeted therapy and chemotherapy. It is also possible to explore a variety of drug delivery methods to improve the uptake of boron-containing agents by tumor sites. Multidisciplinary model is needed to jointly promote BNCT to become a routine clinical treatment modality.

Introduction: The Monte Carlo simulation is used to enhance reliability in the experiments related to nuclear instruments. in addition, that is used to calculate the different components of the neutron and gamma ray fluxes in boron neutron capture therapy(BNCT) and neutron capture (NCT)applications. BNCT is one of the methods in radiotherapy, that is used the neutron beam for kill the cancer cells. The neutron activation analysis(NAA) is the method for identify light elements that the neutron is captured with light elements nucleus and emits characteristic gamma rays. Materials and Methods: the MCNPX code was used for calculation. Boron and other light elements exist in the liver tissue. The BNCT special set geometry was designed. In this designed, light elements analysis is performed simultaneously with the neutron therapy. The effective parameters such as source location, source type, detector location, detector material, patient couch, energy of source, moderator, collimator type, length and thickness of collimator, distance between sample and source, opening of collimator, geometry and location of detector was designed. Results: the best neutron source for BNCT and light element analysis is expanded neutron spectrum produced by the reactor with Paraffin moderator. Neutron Source Generator with every moderator had low efficiency. Collimator made of graphite, graphene and carbon compounds had better neutron output spectrum. Sodium iodide detector is suitable for the detection of light elements gamma rays. The collimator length 20 cm and thickness 6cm. The detectors are placed in a cylindrical arrangement and They should not be exposed to direct neutron radiation. Conclusion: the MCNP study is one of the best methods for BNCT and NCT. the NAA and BNCT is possible Performing Simultaneously. The expanded neutron spectrum from reactors is suitable for NAA and BNCT.