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Objective. To study the secondary neutrons generated by primary oxygen beams for cancer treatment and compare the results to those from primary protons, helium, and carbon ions. This information can provide useful insight into the positioning of neutron detectors in phantom for future experimental dose assessments. Approach. Mono-energetic oxygen beams and spread-out Bragg peaks were simulated using the Monte Carlo particle transport codes FLUktuierende KAskade , tool for particle simulation, and Monte Carlo N-Particle, with energies within the therapeutic range. The energy and angular distribution of the secondary neutrons were quantified. Main results. The secondary neutron spectra generated by primary oxygen beams present the same qualitative trend as for other primary ions. The energy distributions resemble continuous spectra with one peak in the thermal/epithermal region, and one other peak in the fast/relativistic region, with the most probable energy ranging from 94 up to 277 MeV and maximum energies exceeding 500 MeV. The angular distribution of the secondary neutrons is mainly downstream-directed for the fast/relativistic energies, whereas the thermal/epithermal neutrons present a more isotropic propagation. When comparing the four different primary ions, there is a significant increase in the most probable energy as well as the number of secondary neutrons per primary particle when increasing the mass of the primaries. Significance. Most previous studies have only presented results of secondary neutrons generated by primary proton beams. In this work, secondary neutrons generated by primary oxygen beams are presented, and the obtained energy and angular spectra are added as supplementary material. Furthermore, a comparison of the secondary neutron generation by the different primary ions is given, which can be used as the starting point for future studies on treatment plan comparison and secondary neutron dose optimisation. The distal penumbra after the maximum dose deposition appears to be a suitable location for in-phantom dose assessments., (© 2024 Institute of Physics and Engineering in Medicine.)

Purpose: Astronauts on missions beyond low Earth orbit will be exposed to galactic cosmic radiation, and there is concern about potential adverse cardiovascular effects. Most of the research to identify cardiovascular risk of space radiation has been performed in rodent models. To aid in the translation of research results to humans, the current study identified long-term effects of high-energy charged particle irradiation on cardiovascular function and structure in a larger non-rodent animal model., Materials and Methods: At the age of 12 months, male New Zealand white rabbits were exposed to whole-body protons (250 MeV) or oxygen ions ( 16 O, 600 MeV/n) at a dose of 0 or 0.5 Gy and were followed for 12 months after irradiation. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 10- and 12-months post-irradiation. At 12 months after irradiation, blood cell counts and blood chemistry values were assessed, and cardiac tissue and aorta were collected for histological as well as molecular and biochemical analyses. Plasma was used for metabolomic analysis and to quantify common markers of cardiac injury., Results: A small but significant decrease in the percentage of circulating lymphocytes and an increase in neutrophil percentage was seen 12 months after 0.5 Gy protons, while 16 O exposure resulted in an increase in monocyte percentage. Markers of cardiac injury, cardiac troponin I (cTnI) and N-Terminal pro-B-type Natriuretic Peptide were modestly increased in the proton group, and cTnI was also increased after 16 O. On the other hand, metabolomics on plasma at 12 months revealed no changes. Both types of irradiation demonstrated alterations in cardiac mitochondrial morphology and an increase in left ventricular protein levels of inflammatory cell marker CD68. However, changes in cardiac function were only mild., Conclusion: Low dose charged particle irradiation caused mild long-term changes in inflammatory markers, cardiac function, and structure in the rabbit heart, in line with previous studies in mouse and rat models., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

The influence of high-linear energy transfer (LET) particle radiation on the functionalities of mesenchymal stromal cells (MSCs) is largely unknown. Here, we analyzed the effects of proton ( 1 H), helium ( 4 He), carbon ( 12 C) and oxygen ( 16 O) ions on human bone marrow-MSCs. Cell cycle distribution and apoptosis induction were examined by flow cytometry, and DNA damage was quantified using γH2AX immunofluorescence and Western blots. Relative biological effectiveness values of MSCs amounted to 1.0-1.1 for 1 H, 1.7-2.3 for 4 He, 2.9-3.4 for 12 C and 2.6-3.3 for 16 O. Particle radiation did not alter the MSCs' characteristic surface marker pattern, and MSCs maintained their multi-lineage differentiation capabilities. Apoptosis rates ranged low for all radiation modalities. At 24 h after irradiation, particle radiation-induced ATM and CHK2 phosphorylation as well as γH2AX foci numbers returned to baseline levels. The resistance of human MSCs to high-LET irradiation suggests that MSCs remain functional after exposure to moderate doses of particle radiation as seen in normal tissues after particle radiotherapy or during manned space flights. In the future, in vivo models focusing on long-term consequences of particle irradiation on the bone marrow niche and MSCs are needed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Several techniques are under development for image-guidance in particle therapy. Positron (β + ) emission tomography (PET) is in use since many years, because accelerated ions generate positron-emitting isotopes by nuclear fragmentation in the human body. In heavy ion therapy, a major part of the PET signals is produced by β + -emitters generated via projectile fragmentation. A much higher intensity for the PET signal can be obtained using β + -radioactive beams directly for treatment. This idea has always been hampered by the low intensity of the secondary beams, produced by fragmentation of the primary, stable beams. With the intensity upgrade of the SIS-18 synchrotron and the isotopic separation with the fragment separator FRS in the FAIR-phase-0 in Darmstadt, it is now possible to reach radioactive ion beams with sufficient intensity to treat a tumor in small animals. This was the motivation of the BARB (Biomedical Applications of Radioactive ion Beams) experiment that is ongoing at GSI in Darmstadt. This paper will present the plans and instruments developed by the BARB collaboration for testing the use of radioactive beams in cancer therapy., Competing Interests: Author AP was employed by company MedAuston GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Boscolo, Kostyleva, Safari, Anagnostatou, Äystö, Bagchi, Binder, Dedes, Dendooven, Dickel, Drozd, Franczack, Geissel, Gianoli, Graeff, Grahn, Greiner, Haettner, Haghani, Harakeh, Horst, Hornung, Hucka, Kalantar-Nayestanaki, Kazantseva, Kindler, Knöbel, Kuzminchuk-Feuerstein, Lommel, Mukha, Nociforo, Ishikawa, Lovatti, Nitta, Ozoemelam, Pietri, Plaß, Prochazka, Purushothaman, Reidel, Roesch, Schirru, Schuy, Sokol, Steinsberger, Tanaka, Tanihata, Thirolf, Tinganelli, Voss, Weber, Weick, Winfield, Winkler, Zhao, Scheidenberger, Parodi, Durante and the Super-FRS Experiment Collaboration.)

Heavy ion therapy can deliver high doses with high precision. However, image guidance is needed to reduce range uncertainty. Radioactive ions are potentially ideal projectiles for radiotherapy because their decay can be used to visualize the beam. Positron-emitting ions that can be visualized with PET imaging were already studied for therapy application during the pilot therapy project at the Lawrence Berkeley Laboratory, and later within the EULIMA EU project, the GSI therapy trial in Germany, MEDICIS at CERN, and at HIMAC in Japan. The results show that radioactive ion beams provide a large improvement in image quality and signal-to-noise ratio compared to stable ions. The main hindrance toward a clinical use of radioactive ions is their challenging production and the low intensities of the beams. New research projects are ongoing in Europe and Japan to assess the advantages of radioactive ion beams for therapy, to develop new detectors, and to build sources of radioactive ions for medical synchrotrons., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose: Studies are required to determine whether exposures to radiation encountered during manned missions in deep space may have adverse effects on the cardiovascular system. Most of the prior studies on effects of simulated space radiation on the heart and vasculature have been performed in mouse models. To provide data from a second animal species, two studies were performed to assess effects of high-energy charged particle radiation on the heart and abdominal aorta in a rat model., Materials and Methods: In study A, male Long Evans rats were exposed to whole-body protons (250 MeV, 0.5 Gy) or oxygen ions ( 16 O, 600 MeV/n, 0.5 Gy), and ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 3, 5, 9 and 12 months after radiation, followed by tissue collection at 12 months. In study B, male Long Evans rats were exposed to 16 O (1 GeV/n, 0.01-0.25 Gy), and hearts collected at 6 to 7 and 12 months for histology and western-blots., Results: Both protons (250 MeV) and 16 O (600 MeV/n) caused a decrease in left ventricular posterior wall thickness at 3-5 months, but did not change echocardiographic measures of cardiac function. In Pulsed-wave Doppler assessment of the abdominal aorta, an increase was seen in mean velocity, peak velocity, and velocity time integral at 12 months after 16 O (600 MeV/n), suggesting a change in vascular function. There were no significant changes in histopathology or histological quantification of total collagens in heart or aorta. On the other hand, an increase was seen in a 75 kDa peptide of collagen type III in the left ventricle of rats exposed to protons (250 MeV) and 16 O (600 MeV/n and 1 GeV/n), suggesting that radiation caused remodeling of existing collagens in the heart. 16 O (600 MeV/n and 1 GeV/n) caused increases in left ventricular protein levels of immune cell markers CD2, CD4, CD8, and CD68., Conclusion: A single low dose of whole body protons or 16 O in male Long Evans rats did not change cardiac function or induce gross pathological changes in the heart or aorta, but induced mild changes in vascular function and remodeling of existing collagens in the heart. Altogether, studies in prior mouse models and the current work in rats indicate minor changes in cardiac function and structure after a low dose of single-ion radiation., Competing Interests: Declaration of Competing Interests. The authors report no conflicts of interest., (Copyright © 2020 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.)

Purpose: The main advantages of charged particle radiotherapy compared to conventional X-ray external beam radiotherapy are a better tumor conformality coupled with the capability of treating deep-seated radio-resistant tumors. This work investigates the possibility to use oxygen beams for hadron therapy, as an alternative to carbon ions., Materials and Methods: Oxygen ions have the advantage of a higher relative biological effectiveness (RBE) and better conformality to the tumor target. This work describes the mixed radiation field produced by an oxygen beam in water and compares it to the one produced by a therapeutic carbon ion beam. The study has been performed using Geant4 simulations. The dose is calculated for incident carbon ions with energies of 162 MeV/u and 290 MeV/u, and oxygen ions with energies of 192 MeV/u and 245 MeV/u, and hence that the range of the primary oxygen ions projectiles in water was located at the same depth as the carbon ions., Results: The results show that the benefits of oxygen ions are more pronounced when using lower energies because of a slightly higher peak-to-entrance ratio, which allows either providing higher dose in tumor target or reducing it in the surrounding healthy tissues. It is observed that, per incident particle, oxygen ions deliver higher doses than carbon ions., Conclusions: This result coupled with the higher RBE shows that it may be possible to use a lower fluence of oxygen ions to achieve the same therapeutic dose in the patient as that obtained with carbon ion therapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Medical Physics.)