Neutron capture therapy (NCT) is a binary radiotherapeutic modality that relies on the nuclear capture and fission reactions of boron-10 for the selective destruction of cancer cells. Boron delivery agents (BDAs) are used to selectively deliver boron-10 to cancer cells, where it can be activated by neutron irradiation to produce highly cytotoxic alpha particles and recoiling lithium-7 nuclei that cause localized DNA damage and cell death. The development of BDAs for NCT has been an area of active research for several decades, with significant progress made in recent years. Polyhedral boranes, boronated porphyrins, boronated antibodies and peptides, and boronated lipids and nanoparticles are among the most promising BDAs for NCT, each with unique pharmacokinetic properties that make them suitable for specific applications. In addition to the development of novel BDAs, there has also been progress in the optimization of neutron sources and treatment planning strategies for NCT. Clinical trials and preclinical studies have demonstrated the safety and efficacy of NCT with BDAs for the treatment of various cancer types. The promising results of these studies suggest that NCT with BDAs could become an important tool in the fight against cancer. This review links specific boron delivery agent chemotypes to documented tumor-to-normal selectivity data, maps computational modeling approaches directly onto the specific BDA design challenges they have addressed, and summarizes clinical trial outcomes reported to date.

Pancreatic cancer is characterized by late detection, early metastatic dissemination, therapy resistance, and a dense desmoplastic stroma that restricts drug access. Surgical resection with adjuvant chemotherapy confers only modest short-term benefit, but systemic toxicity, acquired chemoresistance, and postoperative relapse constrain long-term survival. Boron neutron capture therapy (BNCT) is a binary radiotherapy in which thermal neutron capture by [10]B triggers the [10]B(n, α)[7]Li reaction, releasing high-linear-energy-transfer alpha particles and lithium-7 nuclei. Their 5-9 μm range confines cytotoxicity to individual cells - an advantage over conventional radiation. However, the clinical boron agents BPA (4‑boronophenylalanine) and BSH (sodium borocaptate) lack selectivity for abdominal tumors and show poor tumor retention. Peptides and small-molecule tumor probes present an alternative delivery strategy for [10]B. Relative to monoclonal antibodies, they are smaller, less immunogenic, easier to synthesize, and penetrate tissue more effectively - properties that enable selective tumor delivery when conjugated with [10]B. Nonetheless, research on such probes as boron carriers has remained relatively limited. This review summarizes recent advances and ongoing challenges in BNCT for pancreatic cancer, focusing on peptide-based and small-molecule tumor probes with high tumor-to-normal tissue (T/N) ratios. It explores their design and application as novel boron carriers to address the targeting limitations of current agents and offers a perspective on advancing the clinical translation of precision BNCT for this disease.

Boron neutron capture therapy (BNCT) is a radiotherapeutic modality that enables tumor-targeted cell killing. The nuclear capture reaction between boron-10 (10B) and low-energy thermal neutrons produces high linear energy transfer (LET) particles (α-particles and recoiling lithium nuclei), each of which have short path lengths within the diameter of a single mammalian cell. The deposited energy creates clustered DNA double-strand breaks that are cytotoxic in these tumor cells while sparing the surrounding healthy tissues. This advantage makes BNCT a highly attractive treatment modality compared to conventional radiotherapy. Nevertheless, despite its theoretical precision, the clinical translation of BNCT remains constrained by suboptimal tumor-selective boron delivery; insufficient intracellular accumulation; and heterogeneous biodistribution profiles associated with conventional small-molecule-based boron agents, such as boronophenylalanine (BPA) and sodium borocaptate (BSH). While the development of new accelerator-based neutron sources (ABNSs) has renewed interest in BNCT, effective 10B delivery remains a major challenge. To address this, nanomedicine has been steadily on the rise in cancer research. In recent years, nanocarrier-based delivery systems have emerged as a transformative alternative delivery strategy. Nanodrugs offer several advantages over conventional small-molecule drugs, such as improved solubility, increased plasma half-life, enhanced permeability and retention in tumors, and active targeting, as well as decreased systemic toxicity and drug resistance. In recent years, nanocarrier-based delivery systems have emerged as a transformative strategy for 10B delivery. In this focused review, we will discuss various types of nanocarriers used for boron drug delivery that enhance boron loading efficiency and evaluate what enables their selective delivery to and accumulation within tumor cells.

Boron neutron capture therapy (BNCT) is a radiotherapeutic modality in which biological selectivity is dictated not by targeting alone but by the spatial control of nuclear reactions. Following tumor-selective accumulation of 10B, neutron irradiation induces the 10B(n,α)7Li reaction, generating high-linear energy transfer particles with micrometer path lengths that confine cytotoxicity to boron-enriched cells. Despite its intrinsic precision, the clinical translation of BNCT has long been hindered by a fundamental chemical challenge: the inability to achieve sufficient, homogeneous, and durable intratumoral boron distribution. In this Account, we argue that BNCT must be reframed as a problem of chemical architecture across length scales, rather than a simple paradigm of boron delivery followed by irradiation. Building on foundational contributions from Jin-Ho Choy (layered double hydroxide-based confinement and ion-exchange systems), Hiroyuki Nakamura (molecular boron design enabling targeting and functional integration), and Koji Ono (clinical dosimetry and translational constraints), we outline how nanohybrid platforms transform BNCT into an integrated systems therapy in which materials design, biological transport, and radiation physics are co-optimized. We identify three governing design principles for next-generation BNCT. First, structural confinement and high-density boron loading enabled by layered inorganic hosts, carborane clusters, and hybrid nanocarriers, ensure sufficient payload delivery at the cellular and subcellular levels. Second, spatiotemporal control of boron distribution, achieved through surface engineering, targeting ligands, and microenvironment-responsive release, addresses the critical challenge of intratumoral heterogeneity. Third, integration with imaging and dosimetry establishes a "measure-what-you-treat" paradigm, linking molecular design directly to therapeutic outcome. We further highlight that BNCT efficacy is governed not by bulk tumor boron concentration alone but by microdistribution and subcellular localization, reflecting the short path length of high-linear energy transfer(LET) particles. This insight shifts design strategies from maximizing systemic delivery toward controlling intracellular fate and spatial precision. In parallel, the transition to accelerator-based neutron sources imposes additional constraints on boron chemistry, necessitating higher delivery efficiency and tighter coordination between pharmacokinetics and irradiation conditions. Together, these advances position BNCT as a chemically programmable precision radiotherapy, in which therapeutic outcome is dictated by the hierarchical organization of boron from molecular to nanoscale to clinical dimensions. Future progress will depend on scalable chemical design, quantitative imaging of boron distribution, and integration with emerging therapeutic modalities. We propose that the next phase of BNCT will be defined by the convergence of nanochemistry, systems-level transport control, and clinically informed design, enabling broader translation into refractory and heterogeneous cancers.

A gated scintillator-based α-particle time-of-flight (αTOF) spectrometer is developed for real-time diagnosis of nuclear reaction products in harsh laser-plasma experiments. The system employs fast-response EJ-204 plastic scintillator coupled with a gated microchannel plate photomultiplier tube and uses gating technique to suppress intense prompt x/γ-ray and relativistic electron radiation backgrounds. Calibration experiments are performed using 100-250 keV protons and 100-300 keV α-particle beams from a 320 kV high-voltage platform. The measured response efficiency increases linearly with particle energy and agrees well with theoretical calculations based on the ionization quenching model. The spectrometer is validated in laser-driven proton-boron fusion experiments at the XG-III laser facility, where a distinct α-particle peak at 3.65 MeV from the dominant 11B(p, α1)8Be* reaction channel is clearly resolved. The results demonstrate that the αTOF spectrometer enables real-time, shot-to-shot acquisition of energy spectra and yield measurements of α particles in high-radiation harsh environments. This work provides a robust online diagnostic tool for laser-driven nuclear reaction studies, with future improvements aimed at extending MeV energy calibration and developing multiplexed detection systems for quantitative yield measurements.

This study presents a combined computational-experimental approach to the design of radiation shields for a metallic Dual-Purpose Casks (DPC) intended for the transport and interim storage of spent fuel. The shield performance was simulated using ORIGEN 2.1 and Top-Mc software and validated against laboratory experiments and MCNP simulations. Initially, using the ORIGEN2.1 code, the neutron and gamma fluxes resulting from nuclear mechanisms were calculated at different cooling times. The results indicate that the isotope Cm-244 after 5 years of cooling, accounts over 98.2% of the spontaneous fission source, 29.9% of the (α, n) reaction mechanism, and 97.6% of the total neutron source, respectively. To evaluate and select the optimal radiation shield, dry storage casks containing 12 spent fuel assemblies were simulated using the Top-Mc software. By incorporating the radioactivity data obtained from ORIGEN2.1 calculations, a suitable composite shield for the transportation and dry storage of spent fuel was developed. The simulations demonstrated that a 10 cm-thick composite shield containing 20% boron carbide reduces the surface dose of the cask to 1.98 mSv/h, in compliance with the radiation safety requirements of SSR-6 standards. For benchmarking purposes, the designed neutron shield was fabricated and experimentally tested in the Tehran Research Reactor (TRR) against a thermal neutron spectrum. The shield achieved 99.69% thermal neutron absorption at a thickness of 0.99 cm. Furthermore, SEM imaging and elemental mapping analysis of the fabricated nanocomposite confirmed the uniform dispersion of filler particles within the polymer matrix. Experimental results were also simulated using MCNP code, revealing a maximum deviation of less than 7% between simulated and actual test conditions.

When calculating dose rates around an Am-Be source, one typically focuses on the neutron emission. In high activity Am-Be sources, there is a need to consider two additional contributors to the dose: low-energy photon emission from the [241]Am decay (59.5 keV and an additional 4.4-MeV photon from the de-excitation of [12]C* (created by the nuclear reaction of the alpha captured by [9]Be). Usually, the dose rate constants (gamma factors) found in the literature provide a good estimation for the dose rates around a point source. For [241]Am however, the gamma-ray dose constant varies significantly (up to 50%) among different publications and is not reproducible by different methods. In order to overcome this challenge, we performed dose calculations using FLUKA - a multipurpose Monte Carlo code for the transport and interaction of elementary particles and heavy ions. This work shows the calculated dose rates around a 1.85-GBq Am-Be source and compared to analytical calculations and results from radiation measurements. It was discovered that the contribution of the photons to the dose rates is in the same order of magnitude as the dose rates from the neutrons.

Boron neutron capture therapy (BNCT) is an emerging cancer treatment modality that has seen a resurgence due to its efficacy and the advent of compact neutron beam devices. BNCT is a binary cancer treatment that combines selective boron delivery with epithermal neutron irradiation. When 10B-enriched compounds accumulate in tumor cells and capture low-energy neutrons, the reaction generates high-linear energy transfer (LET) α-particles and 7Li nuclei that deposit their energy within a few microns, producing irreparable DNA double-strand breaks and tumor cell death while sparing normal tissues. The clinical success of BNCT critically depends on the selective delivery of sufficient boron to tumors. Currently, 4- l-boronophenylalanine (l-BPA) is the leading BNCT agent, as it exploits LAT-1 (SLC7A5), a transporter highly expressed in many solid tumors. However, l-BPA suffers from poor solubility, severely limiting the maximum intravenous dose that can be administered and thereby constraining therapeutic efficacy. Here we report the synthesis and evaluation of highly soluble 10B-enriched l-BPA-based dipeptides as next-generation boron delivery agents. These dipeptides, incorporating hydrophilic peptide linkages, enabled substantially higher intravenous bolus doses in mice compared to l-BPA while maintaining favorable biodistribution. In vivo, the dipeptides were rapidly cleaved by endogenous proteases, releasing l-BPA de novo within tumors. Neutron irradiation of syngeneic CT26 tumors in dipeptide-treated mice produced complete and durable tumor regressions, accompanied by immunological effects including a vaccine response and abscopal tumor suppression. By contrast, l-BPA administered at its solubility-limited maximal dose under the same irradiation conditions produced only a transient tumor growth delay, without durable regression or evidence of immune activation. These findings establish the dipeptides as prodrugs that overcome the solubility limitations of l-BPA, enabling higher-dose administration with improved tumor control and immune-mediated benefits. This strategy has the potential to expand patient management options and enhance the therapeutic impact of BNCT.

An interesting isotope, sulfur-33 (a stable isotope), has been proposed as an additional neutron-capture agent and a cooperative target for improving boron neutron capture therapy. The [33]S (n, α)[30]Si reaction emits the α particles useful for neutron capture therapy. In this study, the dosimetric characteristics of sulfur-33 neutron capture therapy (SNCT) were investigated at the cellular level using the Monte Carlo method. The Monte Carlo N-Particle (MCNP) code was employed to simulate the transport of α particles emitted from different source regions of a single-cell model, including the cell surface (CS), cytoplasm (Cy), and nucleus (N). The model cells were defined as two concentric spheres consisting of the nucleus and cytoplasm. The radius of the cell model was Rc = 6 μm Rn = 3 μm. The S-values (SC←C, SC←CS, SN←N, SN←Cy, SN←CS) were compared to the results with the Medical Internal Radiation Dosimetry (MIRD) method. Finally, S-values of the cellular model of several geometries were calculated.The relative differences of MCNP versus MIRD method S-value for SNCT ranged from 0.28% to 4.29% for C to C (SC←C), -2.82% to 0.05% for Cs to C (SC←Cs), 0.54% to 4.42% for N to N (SN←N), -0.72% to 3.14% for Cy to N (SN ←Cy), and -1.76% to 0.36% for CS to N (SN←CS). The ratios of SN←N/SC←C, SN←CS/SC←C, SN←Cy/SC←C decreased with increasing the cell and nucleus size. The S-value simulated by MCNP is in agreement with the MIRD method, which is proved to be reliable for the cellular dosimetry of SNCT by the Monte Carlo method. The Monte Carlo method can be used instead of the MIRD method to accurately calculate cellular S-value, which solves the problem of cell shape limitation in MIRD method (which is suitable for regular spherical cellular model).

Background: Adult diffuse gliomas represent one of the most aggressive types of brain tumors. Proton therapy offers a minimally invasive treatment option whose biological effectiveness may be enhanced through nuclear reactions involving boron atoms, leading to the emission of high-LET α-particles. In this study, we investigated the potential enhancement of radiation-induced damage of a novel boron-conjugated, ATP-competitive SRC kinase inhibitor, in the U-87 MG glioma cell line and its isogenic cell line stably expressing the IDH1 R132H mutation. Methods: Glioma cells were exposed to either proton or X-ray irradiation to assess whether any enhancement associated with this boron-delivery strategy was specific to proton interactions. Cell survival assays and analyses of DNA damage responses were conducted in both cell lines. Results: While no significant synergistic effects were observed in survival endpoints, differences emerged at the level of early DNA damage effects, with IDH1-mutant glioma cells displaying an enhanced acute response following combined treatment with proton irradiation. Conclusions: These findings support further pharmacological development of boron-based SRC-targeted strategies and underscore the importance of tailoring therapeutic approaches to specific glioma molecular subtypes.

Background: Boron neutron capture therapy (BNCT) represents a highly selective therapeutic modality for recalcitrant cancers, leveraging the nuclear reaction initiated by thermal neutron capture in boron-10 (10B) to deliver high-linear energy transfer radiation (α-particles and 7Li ions) directly within tumor cell boundaries. However, the widespread clinical adoption of BNCT is critically hampered by the pharmacological challenge of achieving sufficiently high, tumor-selective intracellular 10B concentrations (20-50 μg of 10B/g tissue). Conventional small-molecule boron carriers often exhibit dose-limiting non-specificity, rapid systemic clearance, and poor cellular uptake kinetics. Methods: To overcome these delivery barriers, we synthesized and characterized a novel dual-modality nanoplatform based on highly biocompatible, functionalized graphene oxide (GO). This platform was structurally optimized via covalent conjugation with high-boron content carborane clusters (dodecacarborane derivatives) for enhanced BNCT efficacy. Crucially, the nanocarrier was further decorated with plasmonic gold nanostructures (AuNPs), endowing the system with intrinsic surface-enhanced Raman scattering (SERS) properties, enabling real-time, high-resolution intracellular tracking and quantification. Results: We evaluated the synthesized GO@Carborane@Au nanoplatforms for their stability, cytotoxicity, and internalization characteristics. Cytotoxicity assays demonstrated excellent biocompatibility against the non-malignant human keratinocyte line (HaCaT) while showing selective toxicity (upon irradiation, if tested) and high cellular uptake efficiency in the aggressive human glioblastoma tumor cell line (T98G). The integrated plasmonic component allowed for the successful, non-destructive monitoring of nanoplatform delivery and accumulation within both HaCaT and T98G cells using SERS microscopy, confirming the potential for pharmacokinetic and biodistribution studies in vivo. Conclusions: This work details the successful synthesis and preliminary in vitro validation of a unique graphene oxide-based dual-modality nanoplatform designed to address the critical delivery and monitoring challenges of BNCT. By combining highly efficient carborane delivery with an integrated photonic trace marker, this system establishes a robust paradigm for next-generation theranostic agents, significantly advancing the potential for precision, image-guided BNCT for difficult-to-treat cancers like glioblastoma.

The limited global supply of actinium-225 remains a major bottleneck for its widespread clinical application in targeted alpha therapy, highlighting the importance of exploring alternative methods for large-scale production. In this study, the FLUKA and PHITS Monte Carlo transport code was employed to simulate the irradiation of thorium targets with protons, neutrons, and deuterons in the energy range of 20 to 800 MeV per nucleon. The production cross sections of [225]Ac for different incident particles were systematically compared to identify the most promising production pathway for accelerator-based synthesis. Additionally, the study reports production cross section data for actinium, thorium, radium, and protactinium isotopes. By comparing the simulated results with available experimental data, the reliability of the nuclear reaction models was assessed, and directions for further refinement of Monte Carlo-based physical models in radionuclide production simulations were proposed.