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Clinical and Translational Radiation... Sep 2020Modern accelerators have the "flattening filter-free" (FFF) technique to deliver RT with a moderate high-dose rate, currently used in limited clinical indications. No...
INTRODUCTION
Modern accelerators have the "flattening filter-free" (FFF) technique to deliver RT with a moderate high-dose rate, currently used in limited clinical indications. No scientifically established data are currently available on the possible effects of this high dose rate on the anti-tumor immune response. We therefore propose here to study these effects in a preclinical CT26 murine colorectal tumor model.
MATERIAL AND METHODS
, CT26 cells were irradiated on a Varian TrueBeam® linac at 3 different dose rates (4; 12 or 24 Gy/min) using the FFF mode. Activation of the anti-tumor immune response was evaluated by the analysis of induction of genes of the type I interferon pathway by RT-qPCR, and by the study of the induction of immunogenic death biomarkers. , an efficacy study of RT delivering 16.5 Gy at 2 different dose rates was performed in immunocompetent Balb/c mice carrying CT26 syngeneic tumors, as well as an immunomonitoring analysed by flow cytometry and a transcriptomic analysis using RNA sequencing. Statistical analyzes were performed using non-parametric tests.
RESULTS
no significant influence of an increase in FFF dose rate was shown for the induction of genes of the type I interferon pathway as well as for the studied immunogenic death markers (HMGB1 secretion). , no difference in terms of tumor growth retardation between the 2 dose rates used was demonstrated, as well as for the composition of immune cell infiltrates within tumor microenvironment and the expression of immune checkpoints in immunomonitoring and RNAseq.
CONCLUSION
In this study involving the CT26 model, no influence of a moderate high dose rate in FFF technique on the anti-tumor immune response was demonstrated, which would make studies of associations between RT and checkpoint inhibitors fit with this technique of RT. However, further explorations using other cellular models seem to be of interest.
PubMed: 32793819
DOI: 10.1016/j.ctro.2020.07.004 -
Frontiers in Physiology 2023To improve the accuracy of cerebral blood flow (CBF) measurement in mice by accounting for the anesthesia effects. The dependence of CBF on anesthesia dose and time...
To improve the accuracy of cerebral blood flow (CBF) measurement in mice by accounting for the anesthesia effects. The dependence of CBF on anesthesia dose and time was investigated by simultaneously measuring respiration rate (RR) and heart rate (HR) under four different anesthetic regimens. Quantitative CBF was measured by a phase-contrast (PC) MRI technique. RR was evaluated with a mouse monitoring system (MouseOX) while HR was determined using an ultrashort-TE MRI sequence. CBF, RR, and HR were recorded dynamically with a temporal resolution of 1 min in a total of 19 mice. Linear regression models were used to investigate the relationships among CBF, anesthesia dose, RR, and HR. CBF, RR, and HR all showed a significant dependence on anesthesia dose ( < 0.0001). However, the dose in itself was insufficient to account for the variations in physiological parameters, in that they showed a time-dependent change even for a constant dose. RR and HR together can explain 52.6% of the variations in CBF measurements, which is greater than the amount of variance explained by anesthesia dose (32.4%). Based on the multi-parametric regression results, a model was proposed to correct the anesthesia effects in mouse CBF measurements, specifically . We also reported awake-state CBF in mice to be 142.0 ± 8.8 mL/100 g/min, which is consistent with the model-predicted value. The accuracy of CBF measurement in mice can be improved by using a correction model that accounts for respiration rate, heart rate, and anesthesia dose.
PubMed: 37123257
DOI: 10.3389/fphys.2023.1169622 -
Journal of Applied Clinical Medical... Jun 2021To assess dosimetric properties and identify required updates to commonly used protocols (including use of film and ionization chamber) pertaining to a clinical linac...
PURPOSE
To assess dosimetric properties and identify required updates to commonly used protocols (including use of film and ionization chamber) pertaining to a clinical linac configured into FLASH (ultra-high dose rate) electron mode.
METHODS
An 18MV photon beam of a Varian iX linac was converted to FLASH electron beam by replacing the target and the flattening filter with an electron scattering foil. The dose was prescribed by entering the MUs through the console. Fundamental beam properties, including energy, dose rate, dose reproducibility, field size, and dose rate dependence on the SAD, were examined in preparation for radiobiological experiments. Gafchromic EBT-XD film was evaluated for usability in measurements at ultra-high dose rates by comparing the measured dose to the inverse square model. Selected previously reported models of chamber efficiencies were fitted to measurements in a broad range of dose rates.
RESULTS
The performance of the modified linac was found adequate for FLASH radiobiological experiments. With exception of the increase in the dose per MU on increase in the repetition rate, all fundamental beam properties proved to be in line with expectations developed with conventional linacs. The field size followed the theorem of similar triangles. The highest average dose rate (2 × 10 Gy/s) was found next to the internal monitor chamber, with the field size of FWHM = 1.5 cm. Independence of the dose readings on the dose rate (up to 2 × 10 Gy/s) was demonstrated for the EBT-XD film. A model of recombination in an ionization chamber was identified that provided good agreement with the measured chamber efficiencies for the average dose rates up to at least 2 × 10 Gy/s.
CONCLUSION
Dosimetric measurements were performed to characterize a linac converted to FLASH dose rates. Gafchromic EBT-XD film and dose rate-corrected cc13 ionization chamber were demonstrated usable at FLASH dose rates.
Topics: Electrons; Film Dosimetry; Humans; Particle Accelerators; Radiometry; Reproducibility of Results
PubMed: 34028969
DOI: 10.1002/acm2.13270 -
Journal of Radiation Research Mar 2021The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced....
The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as 'the dose-rate effect'. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70-/- mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.
Topics: Animals; Cell Line; Cell Survival; Cesium Radioisotopes; Clone Cells; Cobalt Radioisotopes; DNA End-Joining Repair; DNA-Activated Protein Kinase; Dose-Response Relationship, Radiation; Gamma Rays; Ku Autoantigen; Mice, SCID; Mice
PubMed: 33372229
DOI: 10.1093/jrr/rraa128 -
Health Physics Nov 2021Tin-117 m (Sn-117m) is used to treat dogs with osteoarthritic joints by radiosynoviorthesis. The decay process for Sn-117m is internal conversion wherein IC electrons...
Tin-117 m (Sn-117m) is used to treat dogs with osteoarthritic joints by radiosynoviorthesis. The decay process for Sn-117m is internal conversion wherein IC electrons and auger electrons provide the therapeutic effect. Additionally, the most prominent gamma emission is 158.6 keV. The effective dose rate received by a person interacting at close distances with a treated dog is needed to determine the person's total dose and thus regulatory compliance. Simple measurement of the dose rate at a given distance does not provide an accurate measurement of the effective dose to a person due to the non-uniform nature of the radiation field at close distances. MNCP models of the interactions of five ages of humans at three distances were created to determine the effective dose rates using the methodology from NRC Regulatory Guide 8.40. Ratios of the effective dose rate to the person to the measured dose rate at 1 m from the same source were calculated.
Topics: Animals; Dogs; Electrons; Gamma Rays; Radiation Dosage
PubMed: 34411058
DOI: 10.1097/HP.0000000000001448 -
Vaccines Mar 2023Mathematical studies exploring the impact of booster vaccine doses on the recent COVID-19 waves are scarce, leading to ambiguity regarding the significance of booster...
BACKGROUND
Mathematical studies exploring the impact of booster vaccine doses on the recent COVID-19 waves are scarce, leading to ambiguity regarding the significance of booster doses.
METHODS
A mathematical model with seven compartments was used to determine the basic and effective reproduction numbers and the proportion of infected people during the fifth wave of COVID-19. Using the next-generation matrix, we computed the effective reproduction parameter, Rt.
RESULTS
During the fifth COVID-19 wave, the basic reproductive number in Thailand was calculated to be R0= 1.018691. Analytical analysis of the model revealed both local and global stability of the disease-free equilibrium and the presence of an endemic equilibrium. A dose-dependent decrease in the percentage of infected individuals was observed in the vaccinated population. The simulation results matched the real-world data of the infected patients, establishing the suitability of the model. Furthermore, our analysis suggested that people who had received vaccinations had a better recovery rate and that the death rate was the lowest among those who received the booster dose. The booster dose reduced the effective reproduction number over time, suggesting a vaccine efficacy rate of 0.92.
CONCLUSION
Our study employed a rigorous analytical approach to accurately describe the dynamics of the COVID-19 fifth wave in Thailand. Our findings demonstrated that administering a booster dose can significantly increase the vaccine efficacy rate, resulting in a lower effective reproduction number and a reduction in the number of infected individuals. These results have important implications for public health policymaking, as they provide useful information for the more effective forecasting of the pandemic and improving the efficiency of public health interventions. Moreover, our study contributes to the ongoing discourse on the effectiveness of booster doses in mitigating the impact of the COVID-19 pandemic. Essentially, our study suggests that administering a booster dose can substantially reduce the spread of the virus, supporting the case for widespread booster dose campaigns.
PubMed: 36992172
DOI: 10.3390/vaccines11030589 -
Translational Cancer Research Jul 2021Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. While it has been established that stereotactic body radiotherapy for NSCLC plays an...
Impact of high-dose rate radiotherapy on B and natural killer (NK) cell polarization in peripheral blood mononuclear cells (PBMCs) via inducing non-small cell lung cancer (NSCLC)-derived exosomes.
BACKGROUND
Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. While it has been established that stereotactic body radiotherapy for NSCLC plays an important role in antitumor immune response, the possible effects of the dose rate on this response has not been fully clarified.
METHODS
, A549 cells were irradiated on a Varian TrueBeam Linear Accelerator with dose and dose rate escalation using the flattening filter-free (FFF) technique, which was followed by coculturing with peripheral blood mononuclear cells (PBMCs). The exosomes from irradiated A549 cells were isolated and then cocultured with PBMCs. Flow cytometry was performed to analyze the proportion of lymph cell clusters in PBMCs.
RESULTS
The proportion of CD3- immune cell clusters in PBMCs was significantly higher in the 10 Gy treatment group than in the nonirradiated group and other lower-dose (2, 6 Gy) treatment groups at the dose rate of 1,000 MU/min. However, no influence was observed on the proportion of CD3+ T cell subsets. Further results showed that both natural killer (NK) and B cell proportions reached peaks in the 14 Gy treatment group when a dose rate of 1,200 MU/min was used. Notably, the peak values of these two cell proportions were reached at a lower radiation dose of 10 Gy when a greater dose rate, ranging from 1,600 to 2,400 MU/min, was used. We further found that a single, high dose of irradiation (10 Gy), as compared with a single, low dose of irradiation (2 Gy), could markedly stimulate the A549-related exosome secretion in a radiation dose rate-dependent manner. The ultrahigh dose rate radiation-derived exosomes contributed to the polarization of B and NK cell subsets in PBMCs.
CONCLUSIONS
The optimized radiation regime, which depends on the appropriate radiation dose and dose rate, results in the production of exosomes derived from NSCLC cells and eventually the redistribution of immune cells in PBMCs.
PubMed: 35116657
DOI: 10.21037/tcr-21-536 -
Journal of Medical Physics 2023To investigate the dosimetric performance of newly developed parallel plate chamber in electron beams.
BACKGROUND
To investigate the dosimetric performance of newly developed parallel plate chamber in electron beams.
MATERIALS AND METHODS
Rosalina Instruments India Private Limited (Mumbai, Maharashtra, India) has designed and fabricated PRATT2 parallel plate chamber. The various dosimetric characteristics, including pre- and post-irradiation leakage, stability, polarity effect, chamber response with bias voltage, dose linearity, dose rate effect, and chamber absorbed dose calibration, were performed for the developed chamber. The electron beam energies of 4, 6, 8, and 15MeV were used in this study.
RESULTS
The pre- and post-irradiation leakage of the developed chamber was within the acceptable limit. The chamber shows good stability over the electron beams used in this study. The maximum error in polarity effect was 0.7% for the developed chamber. The chamber shows the good linear response with dose, and its response is independent of the dose rate for all electron beams. The beam quality correction factor (k) was determined for the all electron beam energies, which was used for determination absorbed dose in electron beams.
DISCUSSION
The developed parallel plate chamber (PRATT2) is suitable for dosimetry of electron beams in radiotherapy. The chamber is cost effective and shows precise and reproducible response. The study carried out confirms that the newly designed and fabricated ion chamber can be used in the measurement of absorbed dose for therapeutic electron beams.
PubMed: 38223789
DOI: 10.4103/jmp.jmp_76_23 -
Acta Medica Okayama Apr 2021The forced swim test (FST) induces immobility in mice. Low-dose (high-dose-rate) X-irradiation inhibits FSTinduced immobility in mice due to its antioxidative function....
The forced swim test (FST) induces immobility in mice. Low-dose (high-dose-rate) X-irradiation inhibits FSTinduced immobility in mice due to its antioxidative function. We evaluated the effects of low-dose γ-irradiation at a low-dose-rate on the FST-induced depletion of antioxidants in mouse organs. Mice received whole-body low-dose-rate (0.6 or 3.0 mGy/h) of low-dose γ-irradiation for 1 week, followed by daily FSTs (5 days). The immobility rate on day 2 compared to day 1 was significantly lower in the 3.0 mGy/h irradiated mice than in sham irradiated mice. The FST significantly decreased the catalase (CAT) activity and total glutathione (t-GSH) content in the brain and kidney, respectively. The superoxide dismutase (SOD) activity and t-GSH content in the liver of the 3.0 mGy/h irradiated mice were significantly lower than those of the non-FST-treated mice. The CAT activity in the lungs of mice exposed to 3.0 mGy/h γ-irradiation was higher than that of non-FST treated mice and mice treated with FST. However, no significant differences were observed in the levels of these antioxidant markers between the sham and irradiated groups except for the CAT activity in lungs. These findings suggest that the effects of low-dose-rate and low-dose γ-irradiation on FST are highly organ-dependent.
Topics: Animals; Antioxidants; Dose-Response Relationship, Radiation; Gamma Rays; Immobilization; Mice; Oxidative Stress; Swimming; X-Rays
PubMed: 33953424
DOI: 10.18926/AMO/61896 -
Radiotherapy and Oncology : Journal of... Oct 2023Radiotherapy delivery with ultra-high dose rates (UHDR) has consistently produced normal tissue sparing while maintaining efficacy for tumour control in preclinical...
BACKGROUND AND PURPOSE
Radiotherapy delivery with ultra-high dose rates (UHDR) has consistently produced normal tissue sparing while maintaining efficacy for tumour control in preclinical studies, known as the FLASH effect. Modified clinical electron linacs have been used for pre-clinical studies at reduced source-surface distance (SSD) and novel intra-operative devices are becoming available. In this context, we modified a clinical linac to deliver 16 MeV UHDR electron beams with an isocentric setup.
MATERIALS AND METHODS
The first Varian TrueBeam (SN 1001) was clinically operative between 2009-2022, it was then decommissioned and converted into a research platform. The 18 MeV electron beam was converted into the experimental 16 MeV UHDR. Modifications were performed by Varian and included a software patch, thinner scattering foil and beam tuning. The dose rate, beam characteristics and reproducibility were measured with electron applicators at SSD = 100 cm.
RESULTS
The dose per pulse at isocenter was up to 1.28 Gy/pulse, corresponding to average and instantaneous dose rates up to 256 Gy/s and 3⋅10 Gy/s, respectively. Beam characteristics were equivalent between 16 MeV UHDR and conventional for field sizes up to 10x10cm and an overall beam reproducibility within ± 2.5% was measured.
CONCLUSIONS
We report on the first technical conversion of a Varian TrueBeam to produce 16 MeV UHDR electron beams. This research platform will allow isocenter experiments and deliveries with conventional setups up to field sizes of 10x10 cm within a hospital environment, reducing the gap between preclinical and clinical electron FLASH investigations.
Topics: Humans; Radiotherapy Dosage; Electrons; Reproducibility of Results; Particle Accelerators; Radiometry
PubMed: 37516362
DOI: 10.1016/j.radonc.2023.109822