A Critical Look at Heavy Ion Beam Irradiation for Vaccine Development.

Recent studies offer valuable insights into viral inactivation for vaccine development. Schulze et al. have demonstrated the potential of heavy ion beam irradiation to create effective vaccines, which is particularly relevant in the context of airborne pandemics. Notably, the success in immunizing mice via intranasal administration with the inactivated influenza virus is encouraging, especially given the genetic similarities between influenza and SARS-CoV-2. However, the study raises important considerations. While heavy ion treatment shows advantages, there are concerns about viral inactivation completeness and the potential for surviving viruses, albeit at extremely low levels. Prolonged irradiation times and the risk of selective pressure leading to the evolution of resistant variants are highlighted. Biosafety concerns regarding accidental lab escape of resistant strains are crucial, emphasizing the need for caution during experiments. Moreover, limitations in Monte Carlo simulations of virus irradiation are discussed, pointing out the need for more comprehensive studies to assess the impact of secondary particles on virus inactivation under realistic irradiation conditions. Given these considerations, while the study presents a promising approach for vaccine development, further research is essential to address potential drawbacks and optimize the method for safe and effective application.

A mechanistic simulation of induced DNA damage in a bacterial cell by X- and gamma rays: a parameter study.

Mechanistic Monte Carlo simulations calculating DNA damage caused by ionizing radiation are highly dependent on the simulation parameters. In the present study, using the Geant4-DNA toolkit, the impact of different parameters on DNA damage induced in a bacterial cell by X- and gamma-ray irradiation was investigated. Three geometry configurations, including the simple (without DNA details), the random (a random multiplication of identical DNA segments), and the fractal (a regular replication of DNA segments using fractal Hilbert curves), were simulated. Also, three physics constructors implemented in Geant4-DNA, i.e., G4EmDNAPhysics_option2, G4EmDNAPhysics_option4, and G4EmDNAPhysics_option6, with two energy thresholds of 17.5 eV and 5-37.5 eV were compared for direct DNA damage calculations. Finally, a previously developed mathematical model of cell repair called MEDRAS (Mechanistic DNA Repair and Survival) was employed to compare the impact of physics constructors on the cell survival curve. The simple geometry leads to undesirable results compared to the random and fractal ones, highlighting the importance of simulating complex DNA structures in mechanistic simulation studies. Under the same conditions, the DNA damage calculated in the fractal geometry was more consistent with the experimental data. All physics constructors can be used alternatively with the fractal geometry, provided that an energy threshold of 17.5 eV is considered for recording direct DNA damage. All physics constructors represent a similar behavior in generating cell survival curves, although the slopes of the curves are different. Since the inverse of the slope of a bacterial cell survival curve (i.e., the D10-value) is highly sensitive to the simulation parameters, it is not logical to determine an optimal set of parameters for calculating the D10-value by Monte Carlo simulation.

Radium deposition in human brain tissue: A Geant4-DNA Monte Carlo toolkit study.

NASA has encouraged studies on 226Ra deposition in the human brain to investigate the effects of exposure to alpha particles with high linear energy transfer, which could mimic some of the exposure astronauts face during space travel. However, this approach was criticized, noting that radium is a bone-seeker and accumulates in the skull, which means that the radiation dose from alpha particles emitted by 226Ra would be heavily concentrated in areas close to cranial bones rather than uniformly distributed throughout the brain. In the high background radiation areas of Ramsar, Iran, extremely high levels of 226Ra in soil contribute to a large proportion of the inhabitants' radiation exposure. A prospective study on Ramsar residents with a calcium-rich diet was conducted to improve the dose uniformity due to 226Ra throughout the cerebral and cerebellar parenchyma. The study found that exposure of the human brain to alpha particles did not significantly affect working memory but was significantly associated with increased reaction times. This finding is crucial because astronauts on deep space missions may face similar cognitive impairments due to exposure to high charge and energy particles. The current study was aimed to evaluate the validity of the terrestrial model using the Geant4 Monte Carlo toolkit to simulate the interactions of alpha particles and representative cosmic ray particles, acknowledging that these radiation types are only a subset of the complete space radiation environment.

Monte Carlo Dosimetric Study of Percutaneous Vertebroplasty and Brachytherapy for the Treatment of Spinal Metastases.

Background: Percutaneous vertebroplasty employs bone cement for injecting into the fractured vertebral body (VB) caused by spinal metastases. Radioactive bone cement and also brachytherapy seeds have been utilized to suppress the tumor growth in the VB. Objective: This study aims to investigate the dose distributions of low-energy brachytherapy seeds, and to compare them to those of radioactive bone cement, by Monte Carlo simulation. Material and Methods: In this simulation study, nine CT scan images were imported in Geant4. For the simulation of brachytherapy, I-125, Cs-131, or Pd-103 seeds were positioned in the VB, and for the simulation of vertebroplasty, the VB was filled by a radioactive cement loaded by P-32, Ho-166, Y-90, or Sm-153 radioisotopes. The dose-volume histograms of the VB, and the spinal cord (SC) were obtained after segmentation, considering that the reference dose is the minimum dose covered 95% of the VB. Results: The SC sparing was improved by using beta-emitting cement because of their steep gradient dose distribution. I-125 seeds and Y-90 radioisotope showed better VB coverage for brachytherapy and vertebroplasty techniques, respectively. Pd-103 seeds and P-32 radioisotope showed better SC sparing for brachytherapy and vertebroplasty, respectively. The minimum mean doses that covered 100% of the VB were 62.0%, 56.5%, and 45.0% for I-125, Cs-131, and Pd-103 seeds, and 28.3%, 28.6%, 32.9%, and 17.7%, for P-32, Ho-166, Y-90, and Sm-153 sources, respectively. Conclusion: I-125 and Cs-131 seeds may be useful for large tumors filling the entire VB, and also for the extended tumors invading multiple vertebrae. Beta-emitting bone cement is recommended for tumors located near the SC.

Dosimetric Investigation of Six Ru-106 Eye Plaques by EBT3 Radiochromic Films and Monte Carlo Simulation.

Background: Ophthalmic brachytherapy using radioactive plaques is an effective technique for the treatment of uveal melanoma. Ru-106 eye plaques are considered as interesting issue due to their steep gradient dose. The pre-planning evaluation of dosimetric parameters is essential for the treatment planning system. Objective: The current study aims at providing dose distributions of six Ru-106 eye plaques (CCA, CCB, CGD, CIB, COB and COD) using radiochromic EBT3 film, Geant4 Monte Carlo toolkit and the treatment planning software (Plaque Simulator). Material and Methods: In this experimental study, an in-house phantom was employed for depth dose measurements with EBT3 films. Also, Geant4.10.5 scoring mesh was implemented to obtain the 2D dose distribution of the plaques. The results were compared with Plaque Simulator software and the manufacturer's (BEBIG) data. The gamma index criterion (3%/3 mm) was used to evaluate dose distributions obtained by the film measurements and Geant4 simulation. Results: A good agreement was achieved between simulation and experimental results. Gamma index passing rate was 94.2%, 89.3%, 88.2%, 82.2%, 92.2% and 90.1% for CCA, CCB, CGD, CIB, COB and COD plaques, respectively. Absolute dose rate (mGy/min) obtained by EBT3 film at the depth of 2 mm was 79.4 mGy/min, 81.0 mGy/min, 78.6 mGy/min, 62.2 mGy/min, 75.2 mGy/min and 81.2 mGy/min for CCA, CCB, CGD, CIB, COB and COD plaques, respectively. Conclusion: The measured dose distributions and lateral dose profiles may be utilized in the treatment planning system to cover clinical volumes such as the clinical target volume and the gross tumor volume.

Inactivation of SARS-CoV-2 by charged particles for Future Vaccine Production Applications: A Monte Carlo study.

The world is still suffering from the SARS-CoV-2 pandemic, and the number of infected people is still growing in many countries in 2022. Although great strides have been made to produce effective vaccines, efforts in this field should be accelerated, particularly due to the emergence of new variants. Using inactivated viruses is a conventional method of vaccine production. High levels of ionizing radiation can effectively inactivate viruses. Recently, studies on SARS-CoV-2 irradiation using low-LET radiations (e.g., gamma rays) have been performed. However, there are insufficient studies on the impact of charged particles on the inactivation of this virus. In this study, a realistic structure of SARS-CoV-2 is simulated by using Geant4 Monte Carlo toolkit, and the effect of electrons, protons, alphas, C-12, and Fe-56 ions on the inactivation of SARS-CoV-2 is investigated. The simulation results indicated that densely ionizing (high-LET) particles have the advantage of minimum number of damaged spike proteins per single RNA break. The RNA breaks induced by hydroxyl radicals produced in the surrounding water medium were significant only for electron beam radiation. Hence, indirect RNA breaks induced by densely ionizing particles is negligible. From a simulation standpoint, alpha particles (with energies up to 30 MeV) as well as C-12 ions (with energies up to 80 MeV/n), and Fe-56 ions (with any energy) can be introduced as particles of choice for effective SARS-CoV-2 inactivation.

Revisiting the Paradox of Smoking: Radioactivity in Tobacco Smoke or Suppressing the SARS-CoV-2 Receptor, Angiotensin-Converting Enzyme 2, via Aryl-Hydrocarbon Receptor Signal?

Despite current controversies, some reports show a paradoxical mitigating effect associated with smoking in individuals with symptomatic COVID-19 compared to the general population. To explain the potential mechanisms behind the lower number of hospitalized COVID-19 patients, it has been hypothesized that cigarette smoking may reduce the odds of cytokine storm and related severe inflammatory responses through cholinergic-mediated anti-inflammatory mechanisms. Japanese scientists have recently identified a potential mechanism behind the lower numbers of COVID-19 cases amongst smokers compared to non-smokers. However, we believe that this mitigative effect may be due to the relatively high concentration of deposited energy of alpha particles emitted from naturally occurring radionuclides such as Po-210 in cigarette tobacco. Regarding COVID-19, other researchers and our team have previously addressed the anti-inflammatory and immune-modulating effects of low doses of ionizing radiation. MC-simulation using the Geant4 Monte Carlo toolkit shows that the radiation dose absorbed in a spherical cell with a radius of .9 µm for a single 5.5 MeV alpha particle is about 5.1 Gy. This energy deposition may trigger both anti-inflammatory and anti-thrombotic effects which paradoxically lower the risk of hospitalization due to COVID-19 in smokers.