Search Results (45)

We developed a novel dosimetric method using DNA molecules as a radiation sensor. The amount of neutron or gamma rays irradiated DNA damage was determined by evaluating the amount of DNA serving as a template for qPCR. The absorbed doses in the samples were estimated using the tally of the “t-product” in the data from the PHITS Monte Carlo particle transport simulation code. The neutron fluence for each sample was measured using the niobium activation reaction ⁹³Nb (n, 2n) ^92mNb, and the absorbed dose per neutron fluence was estimated to be 7.1 × 10⁻¹¹ Gy/(n/cm²). Based on the PHITS modeling, the effects of neutron beams are attributed to the combination of proton and alpha particle beams. The results from qPCR showed that neutrons caused more DNA damage than gamma rays. The qPCR method demonstrated that neutron irradiation caused 1.13-fold more DNA damage compared to gamma ray irradiation; however, this result did not show a statistically significant difference. This method we developed, using DNA molecules as a radiation sensor, may be useful for biodosimetry. Full article

Boron Neutron-Capture Therapy (BNCT) is a form of radiation therapy that relies on the highly localized and enhanced biological effects of the ¹⁰B neutron capture (BNC) reaction products to selectively kill cancer cells. The efficacy of BNCT is, therefore, strongly dependent on the ¹⁰B spatial microdistribution at a subcellular level. Fluorescent Nuclear Track Detectors (FNTDs) could be a promising technology for measuring ¹⁰B microdistribution. They allow the measurement of the tracks of charged particles, and their biocompatibility allows cell samples to be deposited and grown on their surfaces. If a layer of borated cells is deposited and irradiated by a neutron field, the energy deposited by the BNC products and their trajectories can be measured by analyzing the corresponding tracks. This allows the reconstruction of the position where the measured particles were generated, hence the microdistribution of ¹⁰B. With respect to other techniques developed to measure ¹⁰B microdistribution, FNTDs would be a non-destructive, biocompatible, relatively easy-to-use, and accessible method, allowing the simultaneous measurement of the ¹⁰B microdistribution, the LET of particles, and the evolution of the related biological response on the very same cell sample. An FNTD was tested in three irradiation conditions to study the feasibility of FNTDs for BNCT applications. The FNTD allowed the successful measurement of the correct alpha particle range and mean penetration depth expected for all the radiation fields employed. This work proved the feasibility of FNTD in reconstructing the tracks of the alpha particles produced in typical BNCT conditions, thus the ¹⁰B microdistribution. Further experiments are planned at the University of Pavia’s LENA (Applied Nuclear Energy Laboratory) to test the final set-up coupling the FNTD with borated cell samples. Full article

Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction ¹⁰B (n, alpha) ⁷Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, “AB-type” Lactosome^® nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o-Carborane (Carb) or 1,2-dihexyl-o-Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the “molecular glue” effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either ¹⁰B-Carb or ¹⁰B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any ¹⁰B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with ¹⁰B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., “theranostics”. Full article

Background/Objective: In this study, for the first time, we examined and compared the sensitivity of four patient-derived cutaneous melanoma cell lines to alpha radiation in vitro and analyzed it in view of cell nucleus area and the formation of double-strand breaks (DSB). Melanoma cells sensitivity to alpha radiation was compared to photon radiation effects. Furthermore, we compared the sensitivity of the melanoma cells to squamous cell carcinoma. Methods: Human melanoma cell lines YDFR.C, DP.C, M12.C, and M16.C, and the squamous cell carcinoma cell line, CAL 27, were irradiated in vitro using Americium-241 as alpha-particle source. Cells were irradiated with doses of 0 to 2.8 gray (Gy). Cell viability, DNA DSB, and nuclear size were measured. Results: 1. Alpha radiation caused death and proliferation arrest of all four melanoma cell lines, but inter-tumor heterogeneity was observed. 2. The most sensitive cell line (DP.C) had a significantly larger nucleus area (408 µm²) and the highest mean number of DSB per cell (9.61) compared to more resistant cells. 3. The most resistant cell, M16.C, had a much lower nucleus area (236.99 µm²) and DSB per cell (6.9). 4. Alpha radiation was more lethal than photon radiation for all melanoma cells. 5. The SCC cell, CAL 27, was more sensitive to alpha radiation than all melanoma cells but had a similar number of DSB (6.67) and nucleus size (175.49 µm²) as the more resistant cells. 6. The cytotoxic effect of alpha radiation was not affected by proliferation arrest after serum starvation. 7. Killing of cells by alpha radiation was marginally elevated by ATR or topoisomerase 1 inhibition. Conclusions: This study demonstrates that various human melanoma cells can be killed by alpha radiation but exhibit variance in sensitivity to alpha radiation. Alpha radiation applied using the Intra-tumoral Diffusing alpha-emitters Radiation Therapy (Alpha DaRT) methodology may serve as an efficient treatment for human melanoma. Full article

Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy. Spherical B NPs with a mode size of 25 nm were prepared by methods of pulsed laser ablation in water, followed by their coating by polyethylene glycol to improve their colloidal stability in buffers. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell killing under irradiation with a 160.5 MeV proton beam. Our experiments showed that the combined effect of B NPs and proton irradiation induces an increased level of superoxide anion radical generation, which leads to the depolarization of mitochondria, a drop in their membrane mitochondrial potential, and the development of apoptosis. A comprehensive gene expression analysis (via RT-PCR) confirmed increased overexpression of 52 genes (out of 87 studied) involved in the cell redox status and oxidative stress, compared to 12 genes in the cells irradiated without B NPs. Other possible mechanisms responsible for the B NPs-induced radiosensitizing effect, including one related to the generation of alpha particles, are discussed. The obtained results give a better insight into the processes involved in the boron-induced enhancement of proton therapy and enable one to optimize parameters of proton therapy in order to maximize therapeutic outcomes. Full article

A Timepix3 detector with a 300$\mathsf{\mu }\mathrm{m}$ silicon sensor has been studied as a novel radiation monitor for the mixed radiation field at the Large Hadron Collider at CERN. This work describes a test campaign carried out at Centro Nacional de Aceleradores with quasi-mono energetic protons (alphas) from 0.6 (1) to 5 (5.6) MeV, where orthogonal irradiations are used to obtain an energy calibration, and a low-energy angular scan to estimate the front dead layer thickness of the sensor. The detector is operated in hole collection mode and at a partial bias of 250$\mathsf{\mu }\mathrm{m}$ at 50 $\mathrm{V}$, which increases the charge sharing among pixels to mitigate the signal saturation at high energy depositions. The data, supported by FLUKA Monte Carlo simulations of energy losses in the sensor, show that the Timepix3 monitor operates in a linear regime up to energy depositions of around 600 $\mathrm{k}$$\mathrm{e}\mathrm{V}$ per pixel and 2 $\mathrm{M}$$\mathrm{e}\mathrm{V}$ per cluster. As a result, the detector has been found to be suitable for measuring charged particle fluxes in the LHC mixed radiation field within the linear calibration regime, with the partial exception of inelastic nuclear reaction hits (mostly from neutrons). Full article

The influence of various energetic particles and electron injection on the transport of minority carriers and non-equilibrium carrier recombination in Ga₂O₃ is summarized in this review. In Ga₂O₃ semiconductors, if robust p-type material and bipolar structures become available, the diffusion lengths of minority carriers will be of critical significance. The diffusion length of minority carriers dictates the functionality of electronic devices such as diodes, transistors, and detectors. One of the problems in ultrawide-bandgap materials technology is the short carrier diffusion length caused by the scattering on extended defects. Electron injection in n- and p-type gallium oxide results in a significant increase in the diffusion length, even after its deterioration, due to exposure to alpha and proton irradiation. Furthermore, post electron injection, the diffusion length of an irradiated material exceeds that of Ga₂O₃ prior to irradiation and injection. The root cause of the electron injection-induced effect is attributed to the increase in the minority carrier lifetime in the material due to the trapping of non-equilibrium electrons on native point defects. It is therefore concluded that electron injection is capable of “healing” the adverse impact of radiation in Ga₂O₃ and can be used for the control of minority carrier transport and, therefore, device performance. Full article

Motivation: Clustered DNA-lesions are predominantly induced by ionizing radiation, particularly by high-LET particles, and considered as lethal damage. Quantification of this specific type of damage as a function of radiation parameters such as LET, dose rate, dose, and particle type can be informative for the prediction of biological outcome in radiobiological studies. This study investigated the induction and complexity of clustered DNA damage for three different types of particles at an LET range of 0.5–250 keV/µm. Methods: Nanometric volumes (36.0 nm³) of 15 base-pair DNA with its hydration shell was modeled. Electron, proton, and alpha particles at various energies were simulated to irradiate the nanometric volumes. The number of ionization events, low-energy electron spectra, and chemical yields for the formation of °OH, H°, ${\mathrm{e}}_{\mathrm{a}\mathrm{q}}^{-}$, and H₂O₂ were calculated for each particle as a function of LET. Single- and double-strand breaks (SSB and DSB), base release, and clustered DNA-lesions were computed from the Monte-Carlo based quantification of the reactive species and measured yields of the species responsible for the DNA lesion formation. Results: The total amount of DNA damage depends on particle type and LET. The number of ionization events underestimates the quantity of DNA damage at LETs higher than 10 keV/µm. Minimum LETs of 9.4 and 11.5 keV/µm are required to induce clustered damage by a single track of proton and alpha particles, respectively. For a given radiation dose, an increase in LET reduces the number of particle tracks, leading to more complex clustered DNA damage, but a smaller number of separated clustered damage sites. Conclusions: The dependency of the number and the complexity of clustered DNA damage on LET and fluence suggests that the quantification of this damage can be a useful method for the estimation of the biological effectiveness of radiation. These results also suggest that medium-LET particles are more appropriate for the treatment of bulk targets, whereas high-LET particles can be more effective for small targets. Full article

Alpha particle-emitting radiopharmaceuticals are in high demand for use in targeted alpha therapy. Ac-225 is currently produced using Th-229, but its annual production remains low, approximately 63 GBq. Previously, we produced a large amount of Ac-225 via the (n,2n) reaction in fast reactors; however, it required repetitive irradiation. In this work, we investigated a method to produce Th-229 via the (3n,x) reaction through long-term irradiation using neutrons from Pressurized Water Reactors. As target nuclides, Ra-226, which is commonly used for Ac-225 production, and Th-230, which is not widely used but is abundant, were selected. The evaluation was conducted under mixed conditions of Th-230 and Th-232. Ra-226 and Th-230 produce Th-229 (T1/2 = 7920 years) after long-term neutron irradiation. Th-229, which has a long half-life, the α-decays to produce Ra-225, and the β-decays of Ra-225 to produce Ac-225. These processes are semi-permanent owing to the long half-life of Th-229. Further, an irradiation method that does not require major changes in the upper part of the PWR fuel assembly geometry was employed by replacing the plugging device attached to the control rod guide tube with a target pin. The PWR loaded with abundant natural thorium target and irradiated with thermal neutrons for as long as approximately 5 years can produce more than twice the current world supply of Ac-225 annually and permanently. Full article

This paper explores the role of microdosimetry in boron neutron capture therapy (BNCT), a cancer treatment involving the selective accumulation of boron-containing compounds in cancer cells, followed by neutron irradiation. Neutron interactions with ¹⁰B induces a nuclear reaction, releasing densely ionizing particles, specifically alpha particles and recoiling lithium-7 nuclei. These particles deposit their energy within a small tissue volume, potentially targeting cancer cells while sparing healthy tissue. The microscopic energy distribution, subject to significant fluctuations due to the short particle range, influences treatment efficacy. Microdosimetry, by studying this distribution, plays a crucial role in optimizing BNCT treatment planning. The methodology employs paired tissue equivalent proportional counters (TEPCs), one with cathode walls enriched with boron and the other without. Precise assessment of boron concentration is essential, as well as the ability to extrapolate results to the actual ¹⁰B concentration within the treatment region. The effective ¹⁰B concentrations within four boronated TEPCs, containing 10, 25, 70, and 100 ppm of ¹⁰B, have been determined. Results show variations of less than 3% from nominal values. Additionally, dose enhancement due to BNC interactions was measured and found to be proportional to the ¹⁰B concentration, with a proportionality factor of 7.7 × 10⁻³ per ppm of boron. Based on these findings, a robust procedure is presented for assessing the impact of BNCT in the treatment region, considering potential variations in boron content relative to the TEPC used. Full article

The spectrometric characteristics of CdZnTe detectors are largely determined by the nonuniformity of the material and the influence of the negative polarization effects associated with the formation of space charges in the sensitive volume of the detector. They change the electric field distribution in the detector and affect the efficiency of the charge carrier collection. An analysis of the waveforms of the output pulses was used to investigate the uniformity of the charge collection and electric field distribution in the detectors when irradiated by the alpha particles. The influence of infrared (IR) illumination on these parameters was evaluated. IR illumination had no positive effect on the planar detector but greatly improved the charge collection in quasi-hemispherical detectors in the peripheral (corner) regions. The output pulse amplitude increased, and the rise time notably decreased. Polarization that occurred predominantly in the corner regions at low temperatures (from −30 °C to −20 °C) was eliminated using IR illumination. Full article

Radiation-hardened semiconductor GaN has drawn considerable attention owing to its excellent properties such as large displacement energy. Many studies have focused on evaluating the degradation of GaN-based power device performance by proton beam or particle irradiation, while quantitative analysis of the energy transfer process of particles inside the material and the mechanisms involved in inducing degradation of electrical properties are rare. Here, on the basis of the fabricated alpha-particle detector, a device model validated by basic electrical experiments is established to simulate the influence of alpha-particle irradiation on the leakage current of the device. We observe that the current does not change significantly with increasing radiation fluence at low bias, while it shows a descending trend with increasing radiation fluence at higher bias. However, increasing the energy of the radiation particles at the same radiation fluence directly leads to a monotonically elevated leakage current. Such a series of phenomena is associated with radiation-induced changes in the density of trapped states within the active layers of the device. Full article

The purpose of the present paper is to clarify, as far as it is possible, the overall picture of experimental results in the field of non-conventional phenomena in nuclear matter published in the scientific literature, accumulated in the past few decades and still missing a widely accepted interpretation. Completeness of the collection of the experiments is not among the aims of the effort; the focus is on adopting a more comprehensive and integral approach through the analysis of the different experimental layouts and different results, searching for common features and analogous factual outcomes in order to obtain a consistent reading of many experimental evidences that appear, so far, to lack a classification in a logic catalogue, which might be compared to a building rather than a collection of single stones. Particular attention is put on the issue of reproducibility of experiments and on the reasons why such a limitation is a frequent characteristic of many experimental activities reported in published papers. This approach is innovative as compared with those already available in the scientific literature. In a synoptical table, a comprehensive classification is given of the twenty experiments examined in terms of types of evidences that are ascertained by the experimenters in their published papers but are “unexpected” according to well-established physical theories. Examples of such unexpected evidences (named also non-conventional or weird) evidences are: excess heat generation, isotope production, reduction of radioactivity levels, and production of neutrons or alpha particles. These evidences are classified taking into account both the material where the evidence takes place (solutions, metals, rocks and artificial materials) and the stimulation techniques (supply of electric voltage, irradiation by photons, mechanical pressure) used to generate the evidences (which do not appear in the absence of such stimuli at an appropriate intensity). Also, in our paper, “identity cards” are provided for each experiment examined, including details that emerged during the experiment and were reported in each respective paper, that sometimes are not given adequate consideration either by the author of the experiment or in other review papers. The analysis of the details provides suggestions (also referred to as clues in this papers) used to formulate the content of the second part of each identity card, where inferences deduced from facts are outlined in view of presenting tentative interpretation at the microscopic level. This is done by concentrating attention on the clues repeated in different experiments in order to yield possible explanations of the “unexpected” evidences. The main outcome of such analysis is that, in all examined cases, a common “operation” can be identified: the stimulation techniques mentioned above can be interpreted as a sort of compression producing a ramp of energy densification (with reference to volumes in space or time coordinates). Here we use the term “compression” to indicate an operation activated by the experimenter; as such, it is objective. We consider energy densification an inference of possible consequences of the operation on the status of the system. Five types of densifications were identified. This reading in terms of energy densification is in accordance with the predictions of the Deformed Space Time theory, reported in the scientific literature, in the context of a generalization of the Einstein relativity theory, according to which the existence of energy thresholds is found to separate, for each interaction, the flat metric part from the deformed metric part and the appearance of new microscopic effects as a consequence of trespassing such thresholds. The phenomena occurring in the deformed part of the interaction metric are governed by the energy density in the space-time (volume and time interval). This energy density is computed from the threshold energies and is peculiar to the phenomenology under consideration. As a conclusion, it is suggested that the revealed qualified information, homogenized and elaborated on, might help in repeating, with proper adjustments and adequate additional instrumentation, some key experiments, in order to ensure systematic reproducibility, which is a prerequisite for interpretations and explanations to be sound and credible, as well in deriving from such an effort, indications for new experiments. It is uncomfortable that, after thirty years, there are still pending questions to which the most acknowledged physical theories are not capable of giving an answer. Even a definitive demonstration that all these experiments have decisive faults would be preferable than leaving the issue unaddressed. Major research agencies, for instance in the USA and in Europe, are moving in this direction. Full article

Boron neutron capture therapy (BNCT) is a binary cancer treatment that involves the irradiation of ¹⁰B-containing tumors with low-energy neutrons (thermal or epithermal). The alpha particles and recoiling Li nuclei that are produced in the ¹⁰B-capture nuclear reaction are high-linear-energy transfer particles that destroy boron-loaded tumor cells; therefore, BNCT has the potential to be a localized therapeutic modality. Two boron-delivery agents have been used in clinical trials of BNCT in patients with malignant brain tumors, cutaneous melanoma, or recurrent tumors of the head and neck region, demonstrating the potential of BNCT in the treatment of difficult cancers. A variety of potentially highly effective boron-delivery agents have been synthesized in the past four decades and tested in cells and animal models. These include boron-containing nucleosides, peptides, proteins, polyamines, porphyrins, liposomes, monoclonal antibodies, and nanoparticles of various types. The most promising agents are multi-functional boronated molecules and nanoparticles functionalized with tumor cell-targeting moieties that increase their tumor selectivity and contain a radiolabel or fluorophore to allow quantification of ¹⁰B-biodistribution and treatment planning. This review discusses multi-functional boron agents reported in the last decade, but their full potential can only be ascertained after their evaluation in BNCT clinical trials. Full article

Radiation-induced bystander effects (RIBE) describe the biological events occurring in non-targeted cells in the vicinity of irradiated ones. Various experimental procedures have been used to investigate RIBE. Interestingly, most micro-irradiation experiments have been performed with alpha particles, whereas most medium transfers have been done with X-rays. With their high fluence, synchrotron X-rays represent a real opportunity to study RIBE by applying these two approaches with the same radiation type. The RIBE induced in human fibroblasts by the medium transfer approach resulted in a generation of DNA double-strand breaks (DSB) occurring from 10 min to 4 h post-irradiation. Such RIBE was found to be dependent on dose and on the number of donor cells. The RIBE induced with the micro-irradiation approach produced DSB with the same temporal occurrence. Culture media containing high concentrations of phosphates were found to inhibit RIBE, while media rich in calcium increased it. The contribution of the RIBE to the biological dose was evaluated after synchrotron X-rays, media transfer, micro-irradiation, and 6 MeV photon irradiation mimicking a standard radiotherapy session: the RIBE may represent less than 1%, about 5%, and about 20% of the initial dose, respectively. However, RIBE may result in beneficial or otherwise deleterious effects in surrounding tissues according to their radiosensitivity status and their capacity to release Ca²⁺ ions in response to radiation. Full article