Transient hypoxia in water irradiated by swift carbon ions at ultra-high dose rates: implication for FLASH carbon-ion therapy

2021 ◽  
Author(s):  
Abdullah Muhammad Zakaria ◽  
Nicholas W. Colangelo ◽  
Jintana Meesungnoen ◽  
Jean-Paul Jay-Gerin
Keyword(s):  
Normal Tissue ◽  
Molecular Mechanisms ◽  
Oxygen Depletion ◽  
Radiation Chemistry ◽  
High Dose ◽  
Carbon Ions ◽  
Human Patient ◽  
Dose Rates ◽  
Depth Dose ◽  
Ion Therapy

Large doses of ionizing radiation delivered to tumors at ultra-high dose rates (i.e., in a few milliseconds) paradoxically spare the surrounding healthy tissue while preserving anti-tumor activity (compared to conventional radiotherapy delivered at much lower dose rates). This new modality is known as “FLASH radiotherapy” (FLASH-RT). Although the molecular mechanisms underlying FLASH-RT are not yet fully understood, it has been suggested that radiation delivered at high dose rates spares normal tissue via oxygen depletion followed by subsequent radioresistance of the irradiated tissue. To date, FLASH-RT has been studied using electrons, photons and protons in various basic biological experiments, pre-clinical studies, and recently in a human patient. However, the efficacy of heavy ions, such as swift carbon ions, under FLASH conditions remains unclear. Given that living cells and tissues consist mainly of water, we set out to study, from a pure radiation chemistry perspective, the effects of ultra-high dose rates on the transient yields and concentrations of radiolytic species formed in water irradiated by 300-MeV per nucleon carbon ions (LET ~ 11.6 keV/μm). This mimics irradiation in the “plateau” region of the depth-dose distribution of ions, i.e., in the “normal” tissue region in which the LET is rather low. We used Monte Carlo simulations of multiple, simultaneously interacting radiation tracks together with an “instantaneous pulse” irradiation model. Our calculations show a pronounced oxygen depletion around 0.2 μs, strongly suggesting, as with electrons, photons and protons, that irradiation with energetic carbon ions at ultra-high dose rates is suitable for FLASH-RT.

scholarly journals The FLASH effect depends on oxygen concentration

2020 ◽  
Vol 93 (1106) ◽  
pp. 20190702 ◽  
Author(s):  
Gabriel Adrian ◽  
Elise Konradsson ◽  
Michael Lempart ◽  
Sven Bäck ◽  
Crister Ceberg ◽  
...  
Keyword(s):  
Oxygen Concentration ◽  
Underlying Mechanism ◽  
Oxygen Depletion ◽  
Therapeutic Window ◽  
High Dose ◽  
Dose Rates ◽  
Conventional Dose ◽  
Oxygen Concentrations

Objective: Recent in vivo results have shown prominent tissue sparing effect of radiotherapy with ultra-high dose rates (FLASH) compared to conventional dose rates (CONV). Oxygen depletion has been proposed as the underlying mechanism, but in vitro data to support this have been lacking. The aim of the current study was to compare FLASH to CONV irradiation under different oxygen concentrations in vitro. Methods: Prostate cancer cells were irradiated at different oxygen concentrations (relative partial pressure ranging between 1.6 and 20%) with a 10 MeV electron beam at a dose rate of either 600 Gy/s (FLASH) or 14 Gy/min (CONV), using a modified clinical linear accelerator. We evaluated the surviving fraction of cells using clonogenic assays after irradiation with doses ranging from 0 to 25 Gy. Results: Under normoxic conditions, no differences between FLASH and CONV irradiation were found. For hypoxic cells (1.6%), the radiation response was similar up to a dose of about 5–10 Gy, above which increased survival was shown for FLASH compared to CONV irradiation. The increased survival was shown to be significant at 18 Gy, and the effect was shown to depend on oxygen concentration. Conclusion: The in vitro FLASH effect depends on oxygen concentration. Further studies to characterize and optimize the use of FLASH in order to widen the therapeutic window are indicated. Advances in knowledge: This paper shows in vitro evidence for the role of oxygen concentration underlying the difference between FLASH and CONV irradiation.

The radiation chemistry of carbon monoxide at very high dose rates

1970 ◽  
Vol 48 (19) ◽  
pp. 3029-3033 ◽  
Author(s):  
C. Willis ◽  
O. A. Miller
Keyword(s):  
Carbon Dioxide ◽  
Carbon Monoxide ◽  
Excited State ◽  
Oxygen Atom ◽  
Dose Rate ◽  
Electron Accelerator ◽  
Radiation Chemistry ◽  
High Dose ◽  
Dose Rates ◽  
Very High

Carbon monoxide has been irradiated with single intense pulses from an electron accelerator at a dose rate of ~ 2 × 1027 eV g−1 s−1. The yield of carbon dioxide obtained was G(CO2) = 0.7 ± 0.1 with a very small yield of carbon suboxide, G(C3O2) ≤ 0.02.Addition of propene reduces the carbon dioxide yield to almost zero while addition of propane has no effect. This suggests that propene is acting as an oxygen atom scavenger rather than as a quencher of an excited state of carbon monoxide. However, rate constant data do not support this suggestion and it is concluded that the residual yield of carbon dioxide observed at high dose rates arises from reaction 9[Formula: see text]where CO+ is in an A2Π or B2Σ+ state.

Cured in a FLASH: Reducing Normal Tissue Toxicities Using Ultra-High-Dose Rates

2019 ◽  
Vol 104 (2) ◽  
pp. 257-260 ◽  
Author(s):  
Hania Al-Hallaq ◽  
Minsong Cao ◽  
Jon Kruse ◽  
Eric Klein
Keyword(s):  
Normal Tissue ◽  
High Dose ◽  
Dose Rates

Radiation chemistry of gaseous oxygen: experimental and calculated yields

1970 ◽  
Vol 48 (10) ◽  
pp. 1505-1514 ◽  
Author(s):  
C. Willis ◽  
A. W. Boyd ◽  
M. J. Young ◽  
D. A. Armstrong
Keyword(s):  
Cross Sections ◽  
Radiation Chemistry ◽  
High Dose Rate ◽  
High Dose ◽  
Gaseous Oxygen ◽  
Dose Rates ◽  
Computer Calculations ◽  
Experimental Yield ◽  
The Difference ◽  
Good Agreement

The yield of ozone from the radiolysis of gaseous oxygen has been measured at 1026–1027 eV g−1 s−1 to be G(O3) = 12.8 ± 0.6, in reasonable agreement with the value of 13.8 of Ghormley, Hochanadel, and Boyle (2a). At 1016 eV g−1 s−1, our results and re-examination of previous data give G(O3) = 6.2 ± 0.6. The same value is obtained at the high dose rates by the addition of electron scavengers. The difference in yields on going from high to low dose rates and the decrease with electron scavengers at the high dose rate is explained by differences in ion neutralization processes. These are supported by computer calculations. The mechanism of the neutralization steps is discussed in terms of the applicability of the electron jump theory and the effect of clustering of the ions.The proportion of energy lost to ionization, excitation, and subexcitation electrons is calculated. This is based on the W value, relative cross sections for ionization, and the potential energy curves for O2+ ions. A predicted yield on this basis is G(O3) = 14.0 ± 0.9, in fairly good agreement with the experimental yield.

scholarly journals Ramipril reduces incidence and prolongates latency time of radiation-induced rat myelopathy after photon and carbon ion irradiation

2020 ◽  
Vol 61 (5) ◽  
pp. 791-798
Author(s):  
Maria Saager ◽  
Eric W Hahn ◽  
Peter Peschke ◽  
Stephan Brons ◽  
Peter E Huber ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Enzyme Inhibitor ◽  
Cervical Spinal Cord ◽  
High Dose ◽  
Latency Time ◽  
Carbon Ions ◽  
Sprague Dawley ◽  
Response Curves ◽  
Radiation Quality ◽  
Radiation Induced

Abstract To test the hypothesis that the use of an angiotensin-converting enzyme inhibitor (ACEi) during radiotherapy may be ameliorative for treatment-related normal tissue damage, a pilot study was conducted with the clinically approved (ACE) inhibitor ramipril on the outcome of radiation-induced myelopathy in the rat cervical spinal cord model. Female Sprague Dawley rats were irradiated with single doses of either carbon ions (LET 45 keV/μm) at the center of a 6 cm spread-out Bragg peak (SOBP) or 6 MeV photons. The rats were randomly distributed into 4 experimental arms: (i) photons; (ii) photons + ramipril; (iii) carbon ions and (iv) carbon ions + ramipril. Ramipril administration (2 mg/kg/day) started directly after irradiation and was maintained during the entire follow-up. Complete dose-response curves were generated for the biological endpoint radiation-induced myelopathy (paresis grade II) within an observation time of 300 days. Administration of ramipril reduced the rate of paralysis at high dose levels for photons and for the first time a similar finding for high-LET particles was demonstrated, which indicates that the effect of ramipril is independent from radiation quality. The reduced rate of myelopathy is accompanied by a general prolongation of latency time for photons and for carbon ions. Although the already clinical approved drug ramipril can be considered as a mitigator of radiation-induced normal tissue toxicity in the central nervous system, further examinations of the underlying pathological mechanisms leading to radiation-induced myelopathy are necessary to increase and sustain its mitigative effectiveness.

scholarly journals Oxygen Depletion in Proton Spot Scanning: A Tool for Exploring the Conditions Needed for FLASH

Radiation ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 290-304
Author(s):  
Bethany C. Rothwell ◽  
Matthew Lowe ◽  
Norman F. Kirkby ◽  
Michael J. Merchant ◽  
Amy L. Chadwick ◽  
...  
Keyword(s):  
Oxygen Depletion ◽  
Spatial And Temporal Variation ◽  
High Dose ◽  
Tumour Control ◽  
Dose Rates ◽  
Oxygen Effects ◽  
In Silico Models ◽  
Hypoxic State ◽  
And Diffusion ◽  
Large Parameter Space

FLASH radiotherapy is a rapidly developing field which promises improved normal tissue protection compared to conventional irradiation and no compromise on tumour control. The transient hypoxic state induced by the depletion of oxygen at high dose rates provides one possible explanation. However, studies have mostly focused on uniform fields of dose and there is a lack of investigation into the spatial and temporal variation of dose from proton pencil-beam scanning (PBS). A model of oxygen reaction and diffusion in tissue has been extended to simulate proton PBS delivery and its impact on oxygen levels. This provides a tool to predict oxygen effects from various PBS treatments, and explore potential delivery strategies. Here we present a number of case applications to demonstrate the use of this tool for FLASH-related investigations. We show that levels of oxygen depletion could vary significantly across a large parameter space for PBS treatments, and highlight the need for in silico models such as this to aid in the development and optimisation of FLASH radiotherapy.

Electron Beam Damage of Biomolecules Assessed by Energy Loss Spectroscopy

1978 ◽  
Vol 36 (3) ◽  
pp. 61-69
Author(s):  
M. Isaacson ◽  
M.L. Collins ◽  
M. Listvan
Keyword(s):  
Electron Microscopy ◽  
Radiation Damage ◽  
Structural Integrity ◽  
Analytical Electron Microscopy ◽  
High Dose ◽  
Dose Rates ◽  
Special Cases ◽  
Analytical Electron ◽  
Atom Migration ◽  
Beam Damage

Over the past five years it has become evident that radiation damage provides the fundamental limit to the study of blomolecular structure by electron microscopy. In some special cases structural determinations at very low doses can be achieved through superposition techniques to study periodic (Unwin & Henderson, 1975) and nonperiodic (Saxton & Frank, 1977) specimens. In addition, protection methods such as glucose embedding (Unwin & Henderson, 1975) and maintenance of specimen hydration at low temperatures (Taylor & Glaeser, 1976) have also shown promise. Despite these successes, the basic nature of radiation damage in the electron microscope is far from clear. In general we cannot predict exactly how different structures will behave during electron Irradiation at high dose rates. Moreover, with the rapid rise of analytical electron microscopy over the last few years, nvicroscopists are becoming concerned with questions of compositional as well as structural integrity. It is important to measure changes in elemental composition arising from atom migration in or loss from the specimen as a result of electron bombardment.

Electron-diffraction studies in synthetic polymer materials

1983 ◽  
Vol 41 ◽  
pp. 362-365
Author(s):  
D.T. Grubb
Keyword(s):  
Electron Diffraction ◽  
Synthetic Polymer ◽  
Polymer Materials ◽  
Crystallographic Structure ◽  
High Dose ◽  
Electron Dose ◽  
Dose Rates ◽  
First Case ◽  
Diffraction Patterns ◽  
The Many

Diffraction studies in polymeric and other beam sensitive materials may bring to mind the many experiments where diffracted intensity has been used as a measure of the electron dose required to destroy fine structure in the TEM. But this paper is concerned with a range of cases where the diffraction pattern itself contains the important information.In the first case, electron diffraction from paraffins, degraded polyethylene and polyethylene single crystals, all the samples are highly ordered, and their crystallographic structure is well known. The diffraction patterns fade on irradiation and may also change considerably in a-spacing, increasing the unit cell volume on irradiation. The effect is large and continuous far C94H190 paraffin and for PE, while for shorter chains to C 28H58 the change is less, levelling off at high dose, Fig.l. It is also found that the change in a-spacing increases at higher dose rates and at higher irradiation temperatures.

Sign in / Sign up

Export Citation Format

Share Document