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The aim of the study was to present various types of radiation that can increase the effectiveness of combined photodynamic therapy (PDT) for malignant and premalignant lesions. Material and Methods. The Web of Science, Scopus, MedLine, Library, and RSCI databases were used for finding publications on this topic, mainly over the last 10 years. Of 230 sources, 64 were included in the review. Results. Photodynamic therapy is a new cancer treatment technology that has become increasingly popular in recent years. It is often an alternative method of treating cancer when there is a high risk of side effects and complications during traditional treatments such as surgery, radiation therapy and chemotherapy. PDT requires a photosensitizer, light energy, and oxygen to create reactive oxygen species that destroy cancer cells. This review examines the basic principles and mechanisms of PDT used alone and in combination with other traditional therapies. Despite the fact that PDT is an effective and non-invasive cancer treatment, it has some limitations, such as low light penetration depth, ineffective photosensitizers and tumor hypoxia. Our study examines new strategies that use other energy sources, such as infrared- and x-rays, ultrasound, as well as electric and magnetic fields, to enhance the PDT effect and overcome its limitations. Great hopes are also associated with the use of a combination of PDT and neutron capture therapy (NСT). Currently, chlorin derivatives associated with boron carriers have been developed. They can be used for both fluorescence diagnostics and PDT, as well as for NСT. The synthesized compounds have a high selectivity of accumulation in the tumor. To date, encouraging preclinical results of high efficiency of combined use of NСT and PDT have already been obtained. Conclusion. Combination with various energy sources is a key factor for further development of PDT. Future research aimed at overcoming the limitations of PDT will contribute to unlocking the full potential of this technology in clinical practice.

Purpose: Neutron capture therapy (NCT) by 10B and 157Gd agents is a unique irradiation‐based method which can be used to treat brain tumors. Current study aims to quantitatively evaluate the relative biological effectiveness (RBE) and dose distributions during the combined BNCT and GdNCT modalities through a hybrid Monte Carlo (MC) simulation approach. Methods: Snyder head phantom as well as a cubic hypothetical tumor was at first modeled by Geant4 MC Code. Then, the energy spectra and dose distribution relevant to the released secondary particles during the combined Gd/BNCT were scored for different concentrations of 157Gd and 10B inside tumor volume. Finally, the scored energy spectra were imported to the MCDS code to estimate both RBESSB and RBEDSB values for different 157Gd concentrations. Results: The results showed that combined Gd/BNCT increases the fluence‐averaged RBESSB values by about 1.7 times when 157Gd concentration increments from 0 to 2000 µg/g for both considered cell oxygen levels (pO2 = 10% and 100%). Besides, a reduction of about 26% was found for fluence‐averaged RBEDSB values with an increment of 157Gd concentration in tumor volume. Conclusion: From the results, it can be concluded that combined Gd/BNCT technique can improve tumor coverage with higher dose levels but in the expense of RBEDSB reduction which can affect the clinical efficacy of the NCT technique. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 1010 atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy is a perspective selective technology for the destruction of cancer cells, while the use of lithium instead of boron may represent a new and promising vector for the development of neutron capture therapy (NCT). The aim of the study was a comparative assessment of the cytotoxicity of various lithium salts, as well as an analysis of the accumulation of lithium in tumor cells in vitro to determine the possibility of using lithium in NCT. The cytotoxicity of lithium salts was determined using MTT‐test and colony forming assay on human fibroblasts BJ‐5ta, human skin melanoma SK‐Mel‐28, and mouse skin melanoma B16 cell lines. An assessment of lithium concentration in cells was performed using inductively coupled plasma atomic emission spectrometry. Our results showed that three different lithium salts at a concentration of 40 μg/ml are not toxic for both tumor and normal cells. The highest uptake values were obtained on murine melanoma B16 cells when exposed to lithium carbonate (0.8 μg/106 cells); however, human melanoma SK‐Mel‐28 cells effectively accumulated both lithium carbonate and lithium citrate (about 0.46 μg/106 cells for two salts). Thus, our results demonstrate a range of non‐toxic doses of lithium salts and a high uptake of lithium by tumor cells, which indicates the possibility to use the lithium in NCT. The use of lithium instead of boron may represent a new and promising vector for the development of neutron capture therapy (NCT). The data obtained in this study demonstrate a range of non‐toxic doses of lithium carbonate, lithium citrate, and lithium chloride, as well as a high uptake of lithium by melanoma cells, that indicates the possibility to use the lithium in NCT. [ABSTRACT FROM AUTHOR]

This study aims to quantitatively evaluate the Relative biological effectiveness (RBE) values relevant to two neutron capture therapy (NCT) techniques with Boron and Gadolinium through a hybrid Monte Carlo (MC) simulation. Variations of 10B and 157Gd concentration in tumor tissue had a negligible impact on the RBE (RBESSB and RBEDSB) values. The obtained RBEDSB values for BNCT were remarkably higher than those of GdNCT. On the other hand, RBESSB values of GdNCT were greater than the obtained values for BNCT. Hence, BNCT has more strength in tumor cell killing due to the higher RBEDSB values. [ABSTRACT FROM AUTHOR]

The expression of marker proteins of acute kidney injury after administration of high doses of lithium carbonate was assessed to evaluate the possibility of lithium use in neutron capture therapy. In mice with implanted skin melanoma B16, the expression of Kim1 (kidney injury molecule 1) and NGAL (neutrophil gelatinase-associated lipocalin) proteins in the kidneys was evaluated immunohistochemically 15, 30, 90, 180 min, and 7 days after peroral administration of lithium carbonate at single doses of 300 and 400 mg/kg. An increase in the expression of the studied proteins was found in 30 and 90 min after administration of 400 mg/kg lithium carbonate, however, 7 days after the drug administration, the expression returned to the level observed in the control group. It can be suggested that single administration of lithium carbonate in the studied doses effective for lithium neutron capture therapy will not significantly affect the renal function. [ABSTRACT FROM AUTHOR]

Neutron capture therapy (NCT) with various concentrations of gadolinium (157Gd) is one of the treatment modalities for glioblastoma (GBM) tumors. Current study aims to evaluate how variations of 157Gd concentration and cell oxygen levels can affect the relative biological effectiveness (RBE) of gadolinium neutron capture therapy (GdNCT) technique through a hybrid Monte Carlo (MC) simulation approach. At first, Snyder phantom including a spherical tumor was simulated by Geant4 MC code and relevant energy electron spectra to different 157Gd concentrations including 100, 250, 500, and 1000 ppm were calculated following the neutron irradiation of simulated phantom. Scored energy electron spectra were then imported to Monte Carlo damage simulation (MCDS) code to estimate RBE values (both RBESSB and RBEDSB) at different gadolinium concentrations and oxygen levels from 10 to 100%. The results indicate that variations of 157Gd can affect the energy spectrum of released secondary electrons including Auger electrons. Variation of gadolinium concentration from 100 to 1000 ppm in tumor region can change RBESSB and RBEDSB values by about 0.1% and 0.5%, respectively. Besides, maximum variations of 4.3% and 2% were calculated for RBEDSB and RBESSB when cell oxygen level changed from 10 to 100%. From the results, variations of considered gadolinium and oxygen concentrations during GdNCT can influence RBE values. Nevertheless, due to the not remarkable changes in the intensity of Auger electrons, a slight difference in RBE values would be expected at various 157Gd concentrations, although considerable RBE changes were calculated relevant to the oxygen alternations inside tumor tissue. [ABSTRACT FROM AUTHOR]

Nano‐sized contrast agents (NCAs) hold potential for highly specific tumor contrast enhancement during magnetic resonance imaging. Given the quantity of contrast agents loaded into a single nano‐carrier and the anticipated relaxation effects, the current molecular design approaches its limits. In this study, a novel molecular mechanism to augment the relaxation of NCAs is introduced and demonstrated. NCA formation is driven by the intramolecular self‐folding of a single polymer chain that possesses systematically arranged hydrophilic and hydrophobic segments in water. Utilizing this self‐folding molecular design, the relaxivity value can be elevated with minimal loading of gadolinium complexes, enabling sharp tumor imaging. Furthermore, the study reveals that this NCA can selectively accumulate into tumor tissues, offering effective anti‐tumor results through gadolinium neutron capture therapy. The efficacy and versatility of this self‐folding molecular design underscore its promise for cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 1010 atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting.

Abstract Nano‐sized contrast agents (NCAs) hold potential for highly specific tumor contrast enhancement during magnetic resonance imaging. Given the quantity of contrast agents loaded into a single nano‐carrier and the anticipated relaxation effects, the current molecular design approaches its limits. In this study, a novel molecular mechanism to augment the relaxation of NCAs is introduced and demonstrated. NCA formation is driven by the intramolecular self‐folding of a single polymer chain that possesses systematically arranged hydrophilic and hydrophobic segments in water. Utilizing this self‐folding molecular design, the relaxivity value can be elevated with minimal loading of gadolinium complexes, enabling sharp tumor imaging. Furthermore, the study reveals that this NCA can selectively accumulate into tumor tissues, offering effective anti‐tumor results through gadolinium neutron capture therapy. The efficacy and versatility of this self‐folding molecular design underscore its promise for cancer diagnosis and treatment.

In the work the computer model of a cell of a system for generating fluxes of therapeutic beams of delayed neutrons, based on the use of delayed fission neutrons, was developed in the Geant 4 environment. The principle of such a neutron source is that when a powerful electron beam interacts with a combined tungsten target and a target containing fissile material, a fission reaction occurs; as a result of which neutrons are emitted. If we move a target activated in this way several tens of meters into a neutron flux generation system consisting of a heater, protection, collimator and reflector, we will obtain a compact neutron source for nuclear medicine. A significant advantage of such a neutron source is the absence of gamma background from the electron accelerator and the combined target, and a bulky protection system is not required. In the Geant 4 environment, the geometry of this cell was developed and a series of experiments were carried out with 107 neutrons. The QGSP BIC HP physical sheet was used. A study of neutron energy spectra showed that more than half of the neutrons whose fluxes are formed using such a cell of the formation system have an energy

In Colombia, medical physics started formally about 3 decades ago. Two master's programs in medical physics initiated activities at two different universities. In particular, the master's program at the Pontificia Universidad Javeriana has been underway since 2012, and taking into account its projections, a team was established in 2015 in collaboration with the Universidad Distrital Francisco José de Caldas to conduct basic research on cancer treatment using neutron capture therapy (NCT). The primary goal of our initiative is to create the infrastructure required to adapt new technologies in our universities in the future. The long-term objective is to use neutron radiation to study not only NCT but also biomolecules, membranes, and materials. This will require the commissioning of an actual nuclear facility. Our group has been exclusively focused on carrying out calculations with GEANT4 because of its characteristics as open-source software, its accessibility, and its ample worldwide use and validation in the particle physics, nuclear physics, and medical physics communities. In this work, we present some results of our preliminary design for the ion accelerator column of a compact neutron generator. Also, we present the characterization of the kinematical and dose distributions of boron neutron capture processes using Geant4. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) involves infusion of cancer patients with a tumor-seeking, boron-loaded compound and irradiation by a beam of neutrons, with an energy range of 1 eV–10 keV. Neutron capture in the 10B atoms results in an effective lethal radiation dose to the tumor cells, while sparing the healthy tissue. Recently available accelerator-based irradiation facilities facilitate developing BNCT to a treatment modality. However, the binary principle of BNCT, together with other points, is challenging in designing clinical trials that allow a timely and safe introduction of this innovative targeted modality into clinical practice. We propose a methodological framework to work toward a systematic, coordinated, and internationally accepted and evidence-based approach. [ABSTRACT FROM AUTHOR]

As a neutron capture therapy (NCT) agent, 157Gd garners significant attention due to the largest neutron capture cross section, emission of γ rays and Auger electrons, and facilitation of magnetic resonance imaging-guided NCT. Owing to its high kinetic stability, 1H relaxivity, and facile conjugation to albumin via electrostatic interactions, the negatively charged Gd 3 TCAS 2 complex {TCAS = thiacalix[4]arene- p -tetrasulfonate (TCAS)} was incorporated into albumin nanoparticles (ANPs) in various configurations, including shell, core, and core-shell types, contingent on the positioning of Gd 3 TCAS 2 within the ANP. The characteristics of the ANPs optimized with respect to loading capacity (LC) were explored, all of which demonstrated particle sizes suitable for passive delivery. The LC of Gd 3 TCAS 2 per ANP increased in the following order: shell (1.1 %) < core (1.4 %) < core-shell (8.1 %). The leakage of Gd 3 TCAS 2 after 7 d of storage was approximately 2 % for all ANPs, indicating stable Gd 3 TCAS 2 loading. The 1H relaxivity (e.g., core-shell: r 1 = 10.7 mM–1s–1) surpassed that of the Gd 3 TCAS 2 complex alone (3.15 mM–1s–1). The luminescence emanating from Tb in MCF-7 cells co-cultured with Tb 3 TCAS 2 -loaded ANPs corroborated this cellular uptake. Gd uptake into MCF-7 cells via Gd 3 TCAS 2 -loaded ANPs was most pronounced for core-shell ANP at 1.33 ± 0.06 nmol/106 cells. The cytotoxicity of Gd 3 TCAS 2 -loaded ANPs was mitigated compared to free Gd 3 TCAS 2 (CC50 = 52 µM), with shell and core-shell ANPs demonstrating nearly 100 % cell survival even at 50 µM. Cell viability post thermal neutron irradiation revealed the highest NCT efficacy for free Gd 3 TCAS 2 , attributed to its elevated cellular uptake (15.71 ± 0.57 nmol/106 cells). Core-shell ANP also exhibited a notable reduction in cell viability relative to the control, validating their potential as a promising GdNCT agent. [Display omitted] • Two thiacalixarene (TCAS) ligands sandwich a tri-Gd core to form the Gd 3 TCAS 2 complex. • Gd 3 TCAS 2 is integrated into albumin nanoparticles (ANPs) for MRI-guided neutron capture therapy. • The loading capacity of Gd 3 TCAS 2 in core-shell ANPs reaches 8.1 %, enhancing 1H relaxivity. • Gd uptake into MCF-7 cells via the ANP measures 1.33 ± 0.06 nmol/106 cells. • Cells incorporated with the ANP are effectively killed by thermal neutron irradiation. [ABSTRACT FROM AUTHOR]

China Institute of Atomic Energy (CIAE) is constructing a high current cyclotron-based boron neutron capture therapy (BNCT) system. The designed proton beam intensity of this cyclotron is 1 mA. The RF system of the cyclotron consists of two separate cavities, two 20-kW amplifiers, a 300-W amplifier for the buncher, and one low-level radio frequency (LLRF) system. The LLRF system controls the amplitudes and phases of the two independent cavities and the buncher. The previous analog–digital hybrid LLRF system in CIAE was designed for low beam loading applications. As during the beam commissioning and machine operation, the RF system requires a more powerful, flexible, and reliable real-time LLRF system, the LLRF group decides to design a new LLRF system for this application. At TRIUMF, a digital LLRF system was developed for the prebuncher of the ARIEL project. This state-of-the-art design is extended and utilized for the BNCT LLRF system. In which, the amplitude and phase of the two separate Dees, as well as the buncher for beam injection, will be regulated by a single field-programmable gate array (FPGA). For such a demanding control task, the design shows a promising future, both from real-time response and flexibility points of view. The design ideas, technology features, system structure, hardware and software development, and the desktop test will be presented. [ABSTRACT FROM AUTHOR]

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.