Neutron Capture Therapy Research Articles

Efficient optimization of an accelerator neutron source for neutron capture therapy using genetic algorithms.

In recent years, genetic algorithms have been applied in the field of nuclear technology design, producing superior optimization results compared to traditional methods. They can be employed in the design and optimization of beam shaping assemblies (BSA) BSA to obtain the desired neutron beams. But it should be noted that the direct combination of Monte Carlo methods with genetic algorithms requires a significant amount of computational resources and time. Design and optimize BSA more efficiently to achieve neutron beams that meet specified recommendations. We propose an approach of NSGA II with crucial variables which are identified by multivariate statistical techniques. This approach significantly reduces the problem sizes, thus reducing the time required for optimization. We illustrate this methodology using the example of BSA design for AB-BNCT. The computational efficiency has tripled with crucial variables. By using NSGA II, we obtained optimized models conforming to both the new and old version IAEA BNCT guidelines through a single optimization process and subjected them to phantom analysis. The results demonstrate that models obtained through this method can meet the IAEA recommendations with deep advantage depth (AD) and high absorbed ratio (AR). The genetic algorithm with crucial variables displays tremendous potential in addressing BSA optimization challenges.

Near-Infrared Absorbing Aza-BODIPY Dyes for Optoelectronic Applications.

Organic dyes that absorb light in the visible to near-infrared region have garnered significant interest, owing to their extensive utility in organic photovoltaics and various biomedical applications. Aza-boron-dipyrromethene (Aza-BODIPY) dyes are a class of chromophores with impressive photophysical properties such as tunable absorption from the visible region towards near infrared (NIR) region, high molar absorptivity, and fluorescence quantum yield. In this review, we discuss the developments in the aza-BODIPYs, related to their synthetic routes, photophysical properties and their applications. Their design strategies, modifications in chemical structures, mode/position of attachment, and their impact on photo-physical properties are reviewed. The potential applications of aza-BODIPY derivatives such as organic solar cells, photodynamic therapy, boron-neutron capture therapy, fluorescence sensors, photo-redox catalysis, photoacoustic probes and optoelectronic devices are explained.

The Expression of Markers of Acute Kidney Injury Kim1 and NGAL after Administration of High Doses of Lithium Carbonate in Mice with Engrafted Skin Melanoma B16

The Expression of Markers of Acute Kidney Injury Kim1 and NGAL after Administration of High Doses of Lithium Carbonate in Mice with Engrafted Skin Melanoma B16

Early Stage In Vitro Bioprofiling of Potential Low-Molecular-Weight Organoboron Compounds for Boron Neutron Capture Therapy (BNCT)—Proposal for a Guide

Given the renewed interest in boron neutron capture therapy (BNCT) and the intensified search for improved boron carriers, as well as the difficulties of coherently comparing the carriers described so far, it seems necessary to define a basic set of assays and standardized methods to be used in the early stages of boron carrier development in vitro. The selection of assays and corresponding methods is based on the practical experience of the authors and is certainly not exhaustive, but open to discussion. The proposed tests/characteristics: Solubility, lipophilicity, stability, cytotoxicity, and cellular uptake apply to both low molecular weight (up to 500 Da) and high molecular weight (5000 Da and more) boron carriers. However, the specific methods have been selected primarily for low molecular weight boron carriers; in the case of high molecular weight compounds, some of the methods may need to be adapted.

Compact pixelated scintillator detector investigation for gamma ray detection

Objective. A scintillator is a luminescent material that converts high-energy photons into visible light and is widely used in medical imaging. Different scintillators are applied to gamma imaging in proton therapy and boron neutron capture therapy (BNCT). A pixelated scintillator is suitable for position measurement. The energy resolution, detection efficiency and position measurement of pixelated scintillators coupled to a SiPM were investigated via two kinds of detectors. The goal of this manuscript was to accurately measure the gamma source position through spectrum analysis in selection of energy windows for characteristic gamma lines. Approach. Scintillators were effectively manufactured and encapsulated before testing, especially for the easily deliquescent LaBr3. The compact front-end electronic prototype modules with 2 × 2 array SiPMs in stacked form and 1 × 10 array SiPMs in parallel form were developed for gamma ray energy resolution and efficiency measurements with a radioactive source of 22Na, which had two energy gamma lines at 511 keV and 1274 keV. Energy calibration was used for accurate energy window selection when measuring the position of the gamma source. Main results. Evident inconsistencies were present between different pixels of the same type of scintillator. Thus, an energy calibration method was needed. LaBr3 was the first candidate scintillator for the gamma ray spectrum measurement since it exhibited the best performance with an energy resolution of ∼5%. The recommended size of LaBr3 was 5 × 5 mm2, which had a higher efficiency than the 3 × 3 mm2 size. The gamma count of the multiple mode of the 2 × 2 array was much higher than that of the single mode, while the energy resolution was poorer. Thus, multiple mode was not suitable for gamma ray detection. The 1 × 10 array detector had the potential to measure the gamma ray source position and could be used for proton therapy and BNCT. A small deviation of 0.22 cm was observed in the measurement of the source center position with Energy Window 1 for 511 keV and Energy Window 2 for 1274 keV before the energy calibration. No deviation was observed after energy calibration. Thus, to achieve a higher accuracy position measurement, automatic energy calibration algorithm was coded into data acquisition software. Significance. The characteristic gamma lines produced by particle therapy are abundant and useful for imaging technology. Our developed compact pixelated scintillator detector coupled with SiPMs could measure the gamma spectrum with high resolution. The energy calibration and window selection method could measure the position of the source with high accuracy. Therefore, an advanced imaging device based on the energy spectrum for particle therapy could be potentially attainable.

Simulation of Boron Dose and Irradiation Time in Lung Cancer Treatment with Boron Neutron Capture Therapy (BNCT) Using MCNP-6

<p>Boron Neutron Capture Therapy (BNCT) is a cancer radiation treatment. This approach employs a boron carrier agent in the form of a chemical that is injected into the body and then travels to the cancer cells. In a lung cancer case study, BNCT treatment simulation was carried out using Monte Carlo N Particle (MCNP) software version 6.2. The goal of this study was to determine the most effective boron concentration and irradiation duration in lung cancer therapy utilizing the BNCT method. The geometry based on a phantom model created by Oak Ridge National Laboratory (ORNL). The simulated cancer geometry, which is placed in the right lung's middle lobe. The skin, ribs, and right lung are among the organs at risk. The skin, ribs, and right lung are among the organs at risk. The neutron source for the simulation is the collimator output from the Kartini Nuclear Reactor's thermal column. In this simulation, the variations in boron concentrations were 40 g/g, 45 g/g, 50 g/g, 55 g/g, and 60 g/g of cancer tissue at 5 g/g intervals. The researchers discovered a link between boron injection concentration and irradiation time, with higher boron injection concentrations resulting in shorter irradiation times. The volume of boron injected determines the effective dose absorbed by healthy tissue surrounding cancer cells. The effective boron concentration for lung cancer therapy is 60 g/g, with deterministic cell killing in the rib marrow and right lung. When utilizing a boron concentration of 60 g/g, the irradiation time is 20.4 minutes. Boron concentrations of 60 g/g are projected to create an effective irradiation time for BNCT-based lung cancer therapy based on the ALARA principle due to their shorter duration when compared to other concentration variations.</p>

Hadron therapy in radiation oncology and why BNCT is a paradigm shift

Abstract Purpose Hadrons, i.e. particles that are heavier than electrons, are playing an increasingly important role in radiation oncology. Due to the high investment costs for the necessary infrastructure, this option is only available in specialized centers. Methods This article describes some of the physical properties that make hadrons attractive for external beam radiation therapy (EBRT), but also some of the challenges that need to be considered. Results The importance of linear energy transfer for biological effects is discussed. Conclusions In addition to the use of charged particles, the importance of neutrons for radiotherapy is also highlighted, in particular the properties of boron neutron capture therapy (BNCT), which open up completely new possibilities for the further development of EBRT.

BNCT Pancreatic Cancer Treatment Strategy with glucose-conjugated boron drug

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

4-Iodobenzonitrile as a fluorogenic derivatization reagent for chromatographic analysis of L-p-boronophenylalanine in whole blood samples using Suzuki coupling reaction.

BackgroundL-p-Boronophehylalanine (BPA) is used in boron neutron capture therapy (BNCT), which is a novel selective cancer radiotherapy technique. It is important to measure BPA levels in human blood for effective radiotherapy; a prompt gamma-ray spectrometer, ICP-AES, and ICP-MS have been used for this purpose. However, these methods require sophisticated and expensive apparatuses as well as experienced analysts. Herein, we propose an HPLC-FL method for the determination of BPA after precolumn derivatization. A new fluorogenic reagent for aryl boronic acid derivatives, namely, 4-iodobenzonitrile, was employed for the fluorogenic derivatization of BPA based on the Suzuki coupling reaction. ResultsAfter the fluorogenic derivatization, a fluorescent cyanobiphenyl derivative is formed with maximum fluorescence at 335 nm after excitation at 290 nm. The developed method showed good linearity (r2=0.997) over the concentration range of 0.5-1000 nmol/L, and the detection limit (S/N=3) was 0.26 nmol/L. The proposed method is more sensitive than previously reported methods for the determination of BPA, including the ICP-MS. Finally, the proposed method was successively applied to the measurement of BPA in human whole blood samples with a good recovery rate (≥95.7%) using only 10 μL of blood sample. The proposed method offers a simple and efficient solution for monitoring BPA levels in BNCT-treated patients. Significance4-Iodobenzonitrile was investigated as a new fluorogenic reagent for BPA based on Suzuki coupling. A new HPLC-FL method for BPA in whole blood samples with ultrasensitivity was developed. The developed method is superior in sensitivity to all previously reported methods for BPA. The method requires only a very small sample volume, making it suitable for micro-blood analysis of BPA via fingerstick sampling.

Apatite–Wollastonite (AW) glass ceramic doped with B2O3: Synthesis, structure, SEM, hardness, XRD, and neutron/charged particle attenuation properties

In the study, the influence of doping apatite-wollastonite (AW) glass-ceramics (GCs) with B2O3 on the structural, physical, microstructural, and light and heavy particle interaction properties is presented. Using the solid-state reaction and the cold isostatic press method, pristine AW, 10 wt% (AW-B10), and 20 wt% (AW-B20) B2O3-doped AW GCs were prepared. The prepared GCs were subject to structural, chemical compositional, and surface morphological investigation through standard experimental processes. Furthermore, the neutron (fast and thermal) and charged radiation (electron, proton, alpha, and carbon ion) interactional parameters of the GCs were obtained through standard theoretical models and software. The density of AW (2.91 gcm-3) increases to about 2.957 and 2.986 gcm-3 as B2O3 increases to 10 and 20 wt%, respectively. The presence of boron oxide supported the wollastonite phase to remain glass and suppressed crystallisation in the AW GCs. Doping AW with B2O3 improved the interaction probabilities of the GCs with fast and thermal neutrons, electrons, protons, alpha particles, and carbon ions. B-rich AW is thus potentially useful as a target material in human tissues for boron neutron capture therapy for the management of cancer and tumours, isolating or shielding specific tissues in ion beam therapy processes, and other techniques that require the exposure of human tissues to irradiation.

Field tuning study and RF electromagnetic design of a continuous-wave RFQ with ramped inter-vane voltage for AB-BNCT

A compact radio frequency quadrupole (RFQ) linac for accelerator-based boron neutron capture therapy is being developed at Xi'an Jiaotong University. By adopting a ramped inter-vane voltage in the beam dynamics design, the RFQ could accelerate a continuous wave proton beam to 2.6 MeV over a length of 4 m, effectively decreasing costs and saving space. To meet the beam-dynamics requirements, both the vane width and undercut were optimized during the electromagnetic design. In addition, π-mode stabilization loops were included to increase the mode separation, and fixed tuners with varying diameters were installed to obtain close frequency-tuning sensitivity. It was established that the field unflatness can be controlled within ±1.5% when all tuners remain at their nominal insertion depth. Optimized cooling-channel design was completed, and multi-physics analysis was conducted. The water tuning coefficients of the vane and wall channels were analyzed to establish the ability to fine tune the RFQ during operation.

Boron-Containing Mesoporous Silica Nanoparticles with Effective Delivery and Targeting of Liver Cancer Cells for Boron Neutron Capture Therapy.

Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN. The latter incorporated boric acid (BA) into hydrophobic mesopores, coated with an LB, and modified with SP94 peptide on the LB. SP94-LB@BA-MSN enhanced nano interface tumor-targeting ability but also prevented the premature release of drugs, which is crucial for BNCT because adequate boron content in tumor sites is required. SP94-LB@BA-MSN showed excellent efficacy in the BNCT treatment of HepG-2 cells. In animal studies with tumor-bearing mice, SP94-LB@BA-MSN exhibited a satisfactory accumulation at the tumor site. The boron content reached 40.18 ± 5.41 ppm in the tumor site 4 h after injection, which was 8.12 and 15.51 times higher than those in mice treated with boronated phenylalanine and those treated with BA. For boron, the tumor-to-normal tissue ratio was 4.41 ± 1.13 and the tumor-to-blood ratio was 5.92 ± 0.45. These results indicated that nanoparticles delivered boron to the tumor site effectively while minimizing accumulation in normal tissues. In conclusion, this composite (SP94-LB@BA-MSN) shows great promise as a boron-containing delivery agent for the treatment of hepatocellular carcinoma using BNCT. These findings highlight the potential of MSNs in the field of BNCT.

Boronophenylalanine‐Containing Polydopamine Nanoparticles for Enhanced Combined Boron Neutron Capture Therapy and Photothermal Therapy for Melanoma Treatment

AbstractMelanoma, the most aggressive skin cancer type, is challenging to treat due to its high metastatic potential and low response to conventional therapies. Innovative approaches, including combination therapies, are crucial for enhancing treatment efficacy while minimizing side effects. It is developed boronophenylalanine‐containing polydopaine (B‐PDA) nanoparticles by encapsulating boronophenylalanine in polydopamine through nitrogen‐boronate coordination, targeting both boron neutron capture therapy (BNCT) and photothermal therapy (PTT). With stability and biocompatibility under physiological conditions, these nanoparticles utilize the phenylalanine residues in BPA to target the overexpressed neutral amino acid transporter 1 (LAT1) in melanoma cells, resulting in enhanced cell‐specific targeting. B‐PDA nanoparticles demonstrated significant photothermal effects under external stimulation, inducing localized heating and triggering heterogeneous tumor cell death, thereby enhancing sensitivity to BNCT. Combining BNCT and PTT, the B‐PDA nanoparticles offer a promising strategy for melanoma treatment.

Application of stoichiometric CT number calibration method for dose calculation of tissue heterogeneous volumes in boron neutron capture therapy.

Monte Carlo simulation code is commonly used for the dose calculation of boron neutron capture therapy. In the past, dose calculation was performed assuming a homogeneous mass density and elemental composition inside the tissue, regardless of the patient's age or sex. Studies have shown that the mass density varies with patient to patient, particularly for those that have undergone surgery or radiotherapy. A method to convert computed tomography numbers into mass density and elemental weights of tissues has been developed and applied in the dose calculation process using Monte Carlo codes. A recent study has shown the variation in the computed tomography number between different scanners for low- and high-density materials. The aim of this study is to investigate the effect of the elemental composition inside each calculation voxel on the dose calculation and the application of the stoichiometric CT number calibration method for boron neutron capture therapy planning. Monte Carlo simulation package Particle and Heavy Ion Transport code System was used for the dose calculation. Firstly, a homogeneous cubic phantom with the material set to ICRU soft tissue (four component), muscle, fat, and brain was modelled and the NeuCure BNCT system accelerator-based neutron source was used. The central axis depth dose distribution was simulated and compared between the four materials. Secondly, a treatment plan of the brain and the head and neck region was simulated using a dummy patient dataset. Three models were generated; (1) a model where only the fundamental materials were considered (simple model), a model where each voxel was assigned a mass density and elemental weight using (2) the Nakao20 model, and (3) the Schneider00 model. The irradiation conditions were kept the same between the different models (irradiation time and irradiation field size) and the near maximum (D1%) and mean dose to the organs at risk were calculated and compared. A maximum percentage difference of approximately 5% was observed between the different materials for the homogeneous phantom. With the dummy patient plan, a large dose difference in the bone (greater than 12%) and region near the low-density material (mucosal membrane, 7%-11%) was found between the different models. A stoichiometric CT number calibration method using the newly developed Nakao20 model was applied to BNCT dose calculation. The results indicate the importance of calibrating the CT number to elemental composition for each individual CT scanner for the purpose of BNCT dose calculation along with the consideration of heterogeneity of the material composition inside the defined region of interest.

Neutron Activation Analysis Based on AB-BNCT Treatment Room.

Boron neutron capture therapy (BNCT) is an ideal binary targeted radiotherapy for treating refractory tumors. An accelerator-based BNCT (AB-BNCT) neutron source has attracted more and more attention due to its advantages such as higher neutron yield in the keV energy region, less gamma radiation, and higher safety. In addition to 10B, neutrons also react with other elements in the treatment room during BNCT to produce many activation products. Due to the long half-life of some activation products, there will be residual radiation after the end of treatment and the shutdown of the accelerator, which has adverse effects on radiation workers. Therefore, the ambient dose equivalent rate in the treatment room needs to be evaluated. The AB-BNCT neutron source model proposed by Li is studied in this paper. Based on the Monte Carlo method, the Geant4 platform was used to simulate the dose induced by radionuclides near the Beam Shaping Assembly (BSA) of the source. It is concluded that the concrete wall contributed the most to the radiation dose. The dose rate of 2.45 μSv h-1 after 13 min of shutdown meets the dose rate limit of 2.5 μSv h-1, at which point it is safe for workers to enter the treatment room area.

Carborane-FAPI conjugate: A potential FAP-targeted boron agent with improved boron content

Boron neutron capture therapy (BNCT) has received extensive attention as an advanced binary radiotherapy method. However, BNCT still faces poor selectivity of boron agent and is insufficient boron content in tumor tissues. To improve the tumor-targeted ability and boron content, this research aims to design, synthesize and preliminary evaluate a new borane agent Carborane-FAPI, which coupling the o-carborane to the compound skeleton of a mature fibroblast activating protein (FAP) inhibitor (FAPI). FAP is a tumor-associated antigen. FAP expressed lowly in normal organs and highly expressed in tumors, so it is a potential target for diagnosis and treatment. Boronophenylalanine (BPA) is the most widely investigated BNCT drug in present. Compared with BPA, the boron content of a single molecule is increased and drug targeting is enhanced. The results show that Carboaren-FAPI has low toxicity to normal cells, and selective enrichment in tumor tissues. It is a promising boron drug that has the potential to be used in BNCT.

Nonclinical pharmacodynamics of boron neutron capture therapy using direct intratumoral administration of a folate receptor targeting novel boron carrier

Abstract Background Boron Neutron Capture Therapy (BNCT) is a precise particle radiation therapy known for its unique cellular targeting ability. The development of innovative boron carriers is crucial for the advancement of BNCT technologies. Our previous study demonstrated the potential of PBC-IP administered via Convection-Enhanced Delivery (CED) in an F98 rat glioma model. This approach significantly extended rat survival in neutron irradiation experiments, with half achieving long-term survival, akin to a cure, in a rat brain tumor model. Our commitment to clinical applicability has spurred additional non-clinical pharmacodynamic research, including an investigation into the effects of cannula position and the time elapsed post-CED administration. Methods In comprehensive in vivo experiments conducted on an F98 rat brain tumor model, we meticulously examined the boron distribution and neutron irradiation experiments at various sites and multiple time intervals following CED administration. Results The PBC-IP showed substantial efficacy for BNCT, revealing minimal differences in tumor boron concentration between central and peripheral CED administration, although a gradual decline in intratumoral boron concentration post-administration was observed. Therapeutic efficacy remained robust, particularly when employing cannula insertion at the tumor margin, compared to central injections. Even delayed neutron irradiation showed notable effectiveness, albeit with a slightly reduced survival period. These findings underscore the robust clinical potential of CED-administered PBC-IP in the treatment of malignant gliomas, offering adaptability across an array of treatment protocols. Conclusions This study represents a significant leap forward in the quest to enhance BNCT for the management of malignant gliomas, opening promising avenues for clinical translation.

The current status and future perspectives of clinical boron neutron capture therapy trials

The current status and future perspectives of clinical boron neutron capture therapy trials

Advancing 2D reaction rate measurements in BNCT: Validation of the indirect neutron radiography method

The precise characterization of neutron beams is a cornerstone of Boron Neutron Capture Therapy (BNCT). While Instrumental Neutron Activation Analysis (INAA) is the standard technique for neutron flux measurement, it is limited in its ability to capture two-dimensional (2D) reaction rate distributions. This study aims to validate the Indirect Neutron Radiography (INR) method for 2D reaction rate quantification, addressing critical variables such as temperature sensitivity and signal fading. We designed and constructed an optimized INR platform comprising an Imaging Plate (IP), readout device, activation detectors (copper foils), and real-time temperature monitoring. Comprehensive experiments were conducted to investigate the impact of ambient temperature and fading time on IP signal reliability. A robust calibration curve was formulated, linking IP signals to dose deposition metrics, thereby enabling precise reaction rate assessments. The study found that IP signals are minimally sensitive to temperature variations (less than 0.1% change per 1 °C), but are subjected to linear fading over time, necessitating stringent temperature control and time-dependent signal corrections. A mathematical relationship between IP signals and dose deposition was established, represented by Y = 20,500 × x0.01803-21103. Application of the INR method revealed that the depth-dependent reaction rates in copper strips closely aligned with those acquired through INAA, exhibiting a relative deviation of less than 5% within a 4cm depth range inside the phantom. Our findings demonstrate that the INR method offers a robust alternative to traditional INAA for capturing 2D reaction rates, effectively addressing complexities like temperature sensitivity and signal fading. While challenges persist, particularly in the realm of measurement errors, this study lays the groundwork for further methodological refinements and broadens the scope for future research in BNCT neutron beam characterization.

Macrophages as carriers of boron carbide nanoparticles dedicated to boron neutron capture therapy

BackgroundThe use of cells as carriers for the delivery of nanoparticles is a promising approach in anticancer therapy, mainly due to their natural properties, such as biocompatibility and non-immunogenicity. Cellular carriers prevent the rapid degradation of nanoparticles, improve their distribution, reduce cytotoxicity and ensure selective delivery to the tumor microenvironment. Therefore, we propose the use of phagocytic cells as boron carbide nanoparticle carriers for boron delivery to the tumor microenvironment in boron neutron capture therapy.ResultsMacrophages originating from cell lines and bone marrow showed a greater ability to interact with boron carbide (B4C) than dendritic cells, especially the preparation containing larger nanoparticles (B4C 2). Consequently, B4C 2 caused greater toxicity and induced the secretion of pro-inflammatory cytokines by these cells. However, migration assays demonstrated that macrophages loaded with B4C 1 migrated more efficiently than with B4C 2. Therefore, smaller nanoparticles (B4C 1) with lower toxicity but similar ability to activate macrophages proved to be more attractive.ConclusionsMacrophages could be promising cellular carriers for boron carbide nanoparticle delivery, especially B4C 1 to the tumor microenvironment and thus prospective use in boron neutron capture therapy.Graphical