Search Results (203)

The pepper-pot method is a beam diagnostics technique used to measure the transverse beam profile, divergence angle, and envelope in particle accelerators. However, its practical application faces challenges, such as insufficient point recognition accuracy and signal quality degradation in complex environments. Based on the Boron Neutron Capture Therapy (BNCT) facility at the Hefei Comprehensive National Science Center—Energy Research Institute (Anhui Energy Laboratory), this study developed an improved pepper-pot beam diagnostics system to optimize the beam quality of the accelerator ion source. The key innovation is adaptive threshold segmentation for spot segmentation, and the experimental results indicate that the enhanced image segmentation method outperforms traditional methods in terms of segmentation accuracy and robustness. Full article

Cancer remains one of the most pressing global health challenges, driving the need for innovative treatment strategies. Boron neutron capture therapy (BNCT) offers a highly selective approach to destroying cancer cells while sparing healthy tissues. To improve boron delivery, Fe₃O₄@Au nanoparticles were developed and functionalized with a boron-containing carborane compound. Fe₃O₄ nanoparticles were synthesized and covered by gold, followed by (3-Aminopropyl)triethoxysilane (APTES) modification to introduce amino groups for carborane immobilization. Comprehensive characterization using SEM, DLS, FTIR, EDX, Brunauer–Emmett–Teller (BET), and XRD confirmed successful functionalization at each stage. TEM confirmed the final structure and elemental composition of the nanoparticles. BET analysis revealed a surface area of 94.69 m²/g and a pore volume of 0.51 cm³/g after carborane loading. Initial release studies in PBS demonstrated the removal of only loosely bound carborane within 48 h, with FTIR confirming stable retention of the compound on the nanoparticle surface. The modified nanoparticles achieved a stable zeta potential of −20 mV. The particles showed low toxicity within a range of concentrations (0–300 μg Fe/mL) and were efficiently accumulated by U251MG cells. These results demonstrate the potential of the obtained nanoparticles to carry boron and gold for their possible application as a theranostic agent. Full article

In boron neutron capture therapy (BNCT), the intracellular localization and concentration of boron-10 atoms significantly influence therapeutic efficacy. Although various boronic-acid-targeted fluorescent probes have been developed to evaluate BNCT agents, most of these probes emit at short wavelengths and are, therefore, incompatible with common nuclear-staining reagents such as Hoechst 33342 and 4′,6-diamidino-2-phenylindole (DAPI). While our previously reported probe, BS-631, emitted fluorescence above 500 nm, it exhibited limitations in terms of reaction rate and fluorescence intensity. To address these issues, we developed a boronic-acid-targeted fluorescent probe with a longer emission wavelength, rapid reactivity, and strong fluorescence intensity. Herein, we designed and synthesized BTTQ, a probe based on a 2-(2-hydroxyphenyl)benzothiazole core structure. BTTQ exhibited immediate fluorescence upon reaction with 4-borono-L-phenylalanine (BPA), with an emission wavelength of 567 nm and a sufficiently high fluorescence quantum yield for detection. BTTQ quantitatively detected BPA with high sensitivity (quantification limit of 10.27 µM), suitable for evaluating BNCT agents. In addition, BTTQ exhibited selective fluorescence for BPA over metal cations. Importantly, BTTQ enabled fluorescence microscopic imaging of intracellular BPA distribution in living cells co-stained with Hoechst 33342. These results suggest that BTTQ is a promising fluorescent probe for the evaluation of future BNCT agents. Full article

One of the promising research areas involving carborane derivatives is boron neutron capture therapy (BNCT). Due to the high boron atom content in carborane molecules, these compounds are considered potential candidates for BNCT-based cancer treatment. Despite ongoing studies on various biologically active carboranyl-containing compounds, the search continues for substances that meet the stringent requirements of effective BNCT agents. In this study, the synthesis of carboranyl-containing derivatives of β-arylaliphatic acids is described, along with the investigation of their reactivity with primary and secondary amines, as well as with metals and their hydroxides. The molecular structures of the synthesized compounds were confirmed using Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectrometry (LC-MS). Cytotoxicity of the water-soluble compound potassium 3-(2-isopropyl-1,2-dicarba-closo-dodecaboran-1-yl)-3-phenylpropanoate was evaluated using several cell lines, including HdFn and MCF-7. Full article

Heat-stable enterotoxin (STa) is a peptide toxin that induces acute diarrhea by binding to guanylyl cyclase C (GC-C) in intestinal epithelial cells. Interestingly, GC-C is highly expressed not only in intestinal cells but also in certain colorectal cancer cells, such as T84 and Caco-2 cells. This unique expression pattern provides STa as an effective candidate for therapeutic applications in cancer suppression or as a probe for detecting cancer cells. Recently, we developed attenuated forms of several STa analogs, including STa topological isomers, and evaluated their efficacy in detecting GC-C on Caco-2 cells, which enables the use of STa in human applications. Therefore, in this study, we investigated the potential application of a ¹⁰B-labeled STa derivative, [Mpr⁵,D-Lys¹⁶(BSH)]-STp(5–17) topological isomer, in boron neutron capture therapy (BNCT), for establishing a novel therapeutic strategy for colorectal cancer. The ¹⁰B-labeled STa peptide clearly exhibited Caco-2 cell killing activity upon neutron irradiation in a concentration-dependent manner, indicating that STa is an effective candidate drug for BNCT. To our knowledge, this is the first report of using STa in boron neutron capture therapy (BNCT). Full article

Background: Boron Neutron Capture Therapy (BNCT) is a promising cancer treatment that combines tumor-selective boron delivery agents with thermal neutrons to kill cancer cells while sparing normal tissue. BNCT requires boron-containing compounds that exhibit high tumor selectivity and achieve therapeutic boron concentrations within tumor cells. This work focuses on the early development of a novel boron cluster carbohydrate derivative based on the glucosamine structure. Our results indicate that this derivative may have advantages over the typical boron delivery agent used in clinical applications and may significantly improve boron delivery capacity at the cellular level. Methods: The performance of the compound in terms of boron uptake was tested in the U87-MG glioblastoma cell line employing neutron autoradiography imaging and quantification. Results: The compound was non-toxic for cells, and it showed a remarkable capacity to enrich cells with boron. The ratio between boron concentration provided in the culture medium and boron concentration achieved in cells was compared to that obtained with boronophenylalanine (BPA), the gold standard in BNCT. The result demonstrated a significantly better performance compared with BPA, showing that the novel agent can concentrate boron in cells more than in culture medium. Conclusions: The encouraging preliminary results provide a starting point for its potential application in in vivo tests. Full article

Recently, studies on accelerator-based boron neutron capture therapy (AB-BNCT) systems for cancer treatment have attracted the attention of researchers around the world. A neutron source can be obtained through the impingement of high-intensity proton beams emitted from the accelerator onto the target. This process would deposit a large amount of heat within this target. A thermal management system design is needed for AB-BNCT systems to prevent the degradation of the target due to thermal/mechanical loading. However, there are few studies that investigate this topic. In this paper, a cooling channel with a boiling heat transfer mechanism is numerically designed for thermal management in order to remove heat deposited in the Be target of the AB-BNCT system of Heron Neutron Medical Corp. A three-dimensional (3D) CFD methodology with a two-fluid model and an RPI wall boiling model is developed to investigate its availability. Two subcooled boiling experiments from previous works are adopted to validate the present CFD boiling model. This validated model can be confidently applied to assist in thermal management design for the AB-BNCT system. Based on the simulation results under the typical operating conditions of the AB-BNCT system set by Heron Neutron Medical Corp., the present coolant channel employing the boiling heat transfer mechanism can efficiently remove the heat deposited in the Be target, as well as maintain its integrity during long-term operation. In addition, compared with the channel with the single-phase convection traditionally designed for an AB-BNCT system, the boiling heat transfer mechanism can result in a lower peak temperature in the Be target and its corresponding deformation. Full article

This study aimed to investigate the distribution of thermal neutron fluence generated during proton-beam therapy (PBT) scanning, focusing on neutrons produced within the body using Monte Carlo simulations (MCSs). MCSs used the Particle and Heavy Ion Treatment Code System to define a 35 × 35 × 35 cm³ water phantom, and proton-beam energies ranging from 70.2 to 228.7 MeV were investigated. The MCS results were compared with neutron fluence measurements obtained from gold activation analysis, showing good agreement with a difference of 3.54%. The internal thermal neutron distribution generated by PBT was isotropic around the proton-beam axis, with the Bragg peak depth varying between 3.45 and 31.9 cm, while the thermal neutron peak depth ranged from 5.41 to 15.9 cm. Thermal neutron generation depended on proton-beam energy, irradiated particle count, and depth. Particularly, the peak of the thermal neutron fluence did not occur within the treatment target volume but in a location outside the target, closer to the source. This discrepancy between the Bragg peak and the thermal neutron fluence peak is a key finding of this study. These data are crucial for optimizing beam angles to maximize dose enhancement within the target during clinical applications of neutron capture-enhanced particle therapy. Full article

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) is a promising, less-invasive anticancer treatment. However, the development of effective boron-based agents (BNCT probes) remains a critical and challenging issue. Previously, we developed a styrene–maleic acid (SMA) copolymer conjugated with glucosamine, encapsulating boronic acid, which exhibited tumor-targeted distribution via the enhanced permeability and retention (EPR) effect. Building upon this approach, in this study, we designed and synthesized a series of SMA-based polymeric probes for BNCT and evaluated their biological activities, with a particular focus on tumor-targeting properties. Methods: Two SMA-based BNCT nanoprobes, SMA–glucosamine conjugated Borax (SG@B) and SMA-conjugated aminophenylboronic acid encapsulating tavaborole (S-APB@TB), were designed and synthesized. The boron content in the conjugates was quantified using inductively coupled plasma mass spectrometry (ICP-MS), while particle sizes were measured via dynamic light scattering (DLS). In vitro cytotoxicity was assessed using the MTT assay in mouse colon cancer C26 cells. The tissue distribution of the conjugates was analyzed in a mouse sarcoma S180 solid tumor model using ICP-MS. Results: Both SG@B and S-APB@TB formed nanoformulations with average particle sizes of 137 nm and 99 nm, respectively. The boron content of SG@B was 2%, whereas S-APB@TB exhibited a significantly higher boron content of 14.4%. Both conjugates demonstrated dose-dependent cytotoxicity against C26 cells, even in the absence of neutron irradiation. Notably, tissue distribution analysis following intravenous injection revealed higher boron concentrations in plasma and tumor tissues compared to most normal tissues, with S-APB@TB showing particularly favorable tumor accumulation. Conclusions: These findings highlight the tumor-targeting potential of SMA-based BNCT nanoprobes. Further investigations are warranted to advance their clinical development as BNCT agents. Full article

Boron Neutron Capture Therapy is a re-emerging therapy for the treatment of cancer, and the development of new neutron-reactive nuclei carriers with enhanced efficiency is of great importance. In this work we propose three new boron-based solid compounds, of formulas [Ca(H₂O)₆](C₁₄H₈O₆B)₂ (CaSB), [Cu(C₁₄H₈O₆B)] (CuSB), and [Li(C₁₄H₈O₆B)(H₂O)] (LiSB), usable as nanoparticles for the carriage of the ¹⁰B isotope. The copper atom in CuSB was introduced because it is known that its presence magnifies the effect of the radiation on cells. Furthermore, the lithium atom in LiSB also allows us to include the ⁶Li isotope, which can take part in the nuclear reactions, enhancing the efficiency of the anti-cancer treatment. The compounds were characterized with single-crystal X-ray diffraction to compare the densities of the reactive isotopes in the materials, a key parameter related to the efficiency of the materials. In this work, we used a computational method to calculate the dose absorbed by a tumor mass treated with nanoparticles of the compounds in order to select the most efficient one for the therapy. The results reported in this work are encouraging. Full article

Boron neutron capture therapy (BNCT) is a specialized cancer treatment that leverages the high absorption cross-section of boron for thermal neutrons. When boron captures neutrons, it undergoes a nuclear reaction that produces alpha particles and lithium ions, which have high linear energy transfer (LET) and can effectively damage nearby cancer cells while minimizing harm to surrounding healthy tissues. This targeted approach makes BNCT particularly advantageous for treating tumors situated in sensitive areas where traditional radiation therapies may pose risks to critical structures. In this study, the deuterium–deuterium (DD) neutron generator, specifically the DD-110 model (neutron yield Y = 1 × 10¹⁰ n/s), served as the neutron source for BNCT. The fast neutrons produced by this generator were thermalized to the epithermal energy range using a beam-shaping assembly (BSA). The BSA was designed with a moderator composed of 32 cm of MgF₂, a reflector made of 76 cm of Pb, and filters including 3 cm of Pb and 1.52 cm of Bi. A collimator, featuring a 10 cm high Pb cone frustum with a 12 cm aperture diameter, was also employed to optimize beam characteristics. The entire system’s performance was modeled and simulated using the MCNPX code, focusing on parameters both in-air and in-phantom to evaluate its efficacy. The findings indicated that the BSA configuration yielded an optimal thermal-to-epithermal flux ratio (${\phi }_{ther}$/${\phi }_{epth}$) of 0.19, a current-to-flux ratio of 0.87, and a gamma dose-to-epithermal flux ratio of 1.71 × 10⁻¹³ Gy/cm², all aligning with IAEA recommendations. The simulated system showed acceptable ratios for ${\phi }_{ther}$/${\phi }_{epth}$, gamma dose to epithermal flux, and beam collimation. Notably, the advantage depth was recorded at 5.5 cm, with an advantage ratio of 2.29 and an advantage depth dose rate of 4.1 × 10⁻⁴ Gy.Eq/min. The epithermal neutron flux of D110 exceeded D109, but D110’s fast neutron contamination increased ~6.6 times. On the other hand, D110’s gamma contamination decreased by 30%. Based on these findings, optimizing neutron source characteristics is crucial for BNCT efficacy. Future research should focus on developing advanced neutron generators that balance these factors, aiming to produce optimal neutron yields for enhanced treatment outcomes and broader applicability. Full article

BODIPY (Boron-Dipyrromethene) dyes have emerged as versatile fluorescent probes in cellular imaging and therapeutic applications owing to their unique chemical properties, including high fluorescence quantum yield, strong extinction coefficients, and remarkable photostability. This review synthesizes the recent advancements in BODIPY dyes, focusing on their deployment in biological imaging and therapy. The exceptional ability of BODIPY dyes to selectively stain cellular structures enables precise visualization of lipids, proteins, and nucleic acids within live and tumor cells, thereby facilitating enhanced understanding of biochemical processes. Moreover, BODIPY derivatives are increasingly utilized in Photodynamic therapy (PDT) and Photothermal therapies (PTT) for targeting cancer cells, where their capability to generate cytotoxic reactive oxygen species upon light activation offers a promising approach to tumor treatment. Recently, BODIPY derivatives have been used for Boron Neutron Capture Therapy (BNCT) for various tumors, and it is a growing research field. Advancements in nanotechnology have allowed the fabrication of BODIPY dye-based nanomedicines, either alone or with the use of metallic nanoparticles as a matrix offering the development of a new class of bioimaging and theragnostic agents. This review also discusses innovative BODIPY-based formulations and strategies that amplify therapeutic efficacy while minimizing adverse effects, underscoring the potential of these dyes as integral components in next-generation diagnostic and therapeutic modalities. By summarizing current research and future perspectives, this review highlights the critical importance of BODIPY dyes in advancing the fields of cellular imaging and treatment methodologies. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) is a promising approach for selectively targeting and destroying malignant cells using ¹⁰B isotopes. A significant challenge in BNCT lies in the development of efficient boron delivery systems that ensure adequate boron accumulation within tumor cells. This study aims to synthesize, characterize, and evaluate COSAN-functionalized nanoparticles (NP@I-COSAN) as a potential boron carrier for BNCT. Methods: Hybrid nanoparticles were synthesized by conjugating monoiodinated cobaltabisdicarbollides (I-COSAN) to commercially available acrylic polymer-based nanoparticles. Functionalization and cellular uptake were confirmed through FTIR, TGA, UV-Vis spectroscopy, and TEM/EDX analyses. Biocompatibility was evaluated by assessing cytotoxicity in HeLa cells and C. elegans as an in vivo model. Intracellular boron uptake was quantified using ICP-MS, with results compared to those obtained with 4-borono-L-phenylalanine conjugated to fructose (f-BPA). An in vitro BNCT proof-of-concept assay was also performed to evaluate therapeutic efficacy. Results: NP@I-COSAN demonstrated low cytotoxicity and efficient internalization in cells. ICP-MS analysis revealed stable boron retention, comparable to traditional boron agents. The BNCT assay further showed that NP@I-COSAN was effective in inducing tumor cell apoptosis, even at lower boron concentrations than conventional treatments. Conclusions: These results underscore the potential of NP@I-COSAN as an effective boron delivery system for BNCT, offering a promising strategy to enhance boron accumulation within tumor cells and improve treatment efficacy. Full article

Background/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion. Full article