Abstract:Passive dosimetry with radiochromic films is widely used in proton radiotherapy, both in clinical and scientific environments, thanks to its simplicity, high spatial resolution and dose-rate independence. However, film under-response for low-energy protons, the so-called linear-energy transfer (LET) quenching, must be accounted and corrected for. We perform a meta-analysis on existing film under-response data with EBT, EBT2 and EBT3 GAFchromic™ films and provide a common framework to integrate it, based on the… Show more
“…Moreover, some of this radioactive fluorine appears to cluster in the bony structures of the chicken embryo. Indeed, 18 F-NaF is a well-known radiotracer used to monitor osteogenic activity for the detection of osseous metastases 38 . Figure 4 CT (left) and PET (right) maximum intensity projection images of E1.…”
Section: Resultsmentioning
confidence: 99%
“…This code 35 was used to produce suitable treatment plans for sample irradiation and to estimate the amount of absorbed dose from irradiation logs. Quality assurance of the plans was performed by comparing the expected dose with a plan-specific treatment verification film, after correcting for quenching effects 38 .…”
Range verification of clinical protontherapy systems via positron-emission tomography (PET) is not a mature technology, suffering from two major issues: insufficient signal from low-energy protons in the Bragg peak area and biological washout of PET emitters. The use of contrast agents including 18O, 68Zn or 63Cu, isotopes with a high cross section for low-energy protons in nuclear reactions producing PET emitters, has been proposed to enhance the PET signal in the last millimeters of the proton path. However, it remains a challenge to achieve sufficient concentrations of these isotopes in the target volume. Here we investigate the possibilities of 18O-enriched water (18-W), a potential contrast agent that could be incorporated in large proportions in live tissues by replacing regular water. We hypothesize that 18-W could also mitigate the problem of biological washout, as PET (18F) isotopes created inside live cells would remain trapped in the form of fluoride anions (F-), allowing its signal to be detected even hours after irradiation. To test our hypothesis, we designed an experiment with two main goals: first, prove that 18-W can incorporate enough 18O into a living organism to produce a detectable signal from 18F after proton irradiation, and second, determine the amount of activity that remains trapped inside the cells. The experiment was performed on a chicken embryo chorioallantoic membrane tumor model of head and neck cancer. Seven eggs with visible tumors were infused with 18-W and irradiated with 8-MeV protons (range in water: 0.74 mm), equivalent to clinical protons at the end of particle range. The activity produced after irradiation was detected and quantified in a small-animal PET-CT scanner, and further studied by placing ex-vivo tumours in a gamma radiation detector. In the acquired images, specific activity of 18F (originating from 18-W) could be detected in the tumour area of the alive chicken embryo up to 9 h after irradiation, which confirms that low-energy protons can indeed produce a detectable PET signal if a suitable contrast agent is employed. Moreover, dynamic PET studies in two of the eggs evidenced a minimal effect of biological washout, with 68% retained specific 18F activity at 8 h after irradiation. Furthermore, ex-vivo analysis of 4 irradiated tumours showed that up to 3% of oxygen atoms in the targets were replaced by 18O from infused 18-W, and evidenced an entrapment of 59% for specific activity of 18F after washing, supporting our hypothesis that F- ions remain trapped within the cells. An infusion of 18-W can incorporate 18O in animal tissues by replacing regular water inside cells, producing a PET signal when irradiated with low-energy protons that could be used for range verification in protontherapy. 18F produced inside cells remains entrapped and suffers from minimal biological washout, allowing for a sharper localization with longer PET acquisitions. Further studies must evaluate the feasibility of this technique in dosimetric conditions closer to clinical practice, in order to define potential protocols for its use in patients.
“…Moreover, some of this radioactive fluorine appears to cluster in the bony structures of the chicken embryo. Indeed, 18 F-NaF is a well-known radiotracer used to monitor osteogenic activity for the detection of osseous metastases 38 . Figure 4 CT (left) and PET (right) maximum intensity projection images of E1.…”
Section: Resultsmentioning
confidence: 99%
“…This code 35 was used to produce suitable treatment plans for sample irradiation and to estimate the amount of absorbed dose from irradiation logs. Quality assurance of the plans was performed by comparing the expected dose with a plan-specific treatment verification film, after correcting for quenching effects 38 .…”
Range verification of clinical protontherapy systems via positron-emission tomography (PET) is not a mature technology, suffering from two major issues: insufficient signal from low-energy protons in the Bragg peak area and biological washout of PET emitters. The use of contrast agents including 18O, 68Zn or 63Cu, isotopes with a high cross section for low-energy protons in nuclear reactions producing PET emitters, has been proposed to enhance the PET signal in the last millimeters of the proton path. However, it remains a challenge to achieve sufficient concentrations of these isotopes in the target volume. Here we investigate the possibilities of 18O-enriched water (18-W), a potential contrast agent that could be incorporated in large proportions in live tissues by replacing regular water. We hypothesize that 18-W could also mitigate the problem of biological washout, as PET (18F) isotopes created inside live cells would remain trapped in the form of fluoride anions (F-), allowing its signal to be detected even hours after irradiation. To test our hypothesis, we designed an experiment with two main goals: first, prove that 18-W can incorporate enough 18O into a living organism to produce a detectable signal from 18F after proton irradiation, and second, determine the amount of activity that remains trapped inside the cells. The experiment was performed on a chicken embryo chorioallantoic membrane tumor model of head and neck cancer. Seven eggs with visible tumors were infused with 18-W and irradiated with 8-MeV protons (range in water: 0.74 mm), equivalent to clinical protons at the end of particle range. The activity produced after irradiation was detected and quantified in a small-animal PET-CT scanner, and further studied by placing ex-vivo tumours in a gamma radiation detector. In the acquired images, specific activity of 18F (originating from 18-W) could be detected in the tumour area of the alive chicken embryo up to 9 h after irradiation, which confirms that low-energy protons can indeed produce a detectable PET signal if a suitable contrast agent is employed. Moreover, dynamic PET studies in two of the eggs evidenced a minimal effect of biological washout, with 68% retained specific 18F activity at 8 h after irradiation. Furthermore, ex-vivo analysis of 4 irradiated tumours showed that up to 3% of oxygen atoms in the targets were replaced by 18O from infused 18-W, and evidenced an entrapment of 59% for specific activity of 18F after washing, supporting our hypothesis that F- ions remain trapped within the cells. An infusion of 18-W can incorporate 18O in animal tissues by replacing regular water inside cells, producing a PET signal when irradiated with low-energy protons that could be used for range verification in protontherapy. 18F produced inside cells remains entrapped and suffers from minimal biological washout, allowing for a sharper localization with longer PET acquisitions. Further studies must evaluate the feasibility of this technique in dosimetric conditions closer to clinical practice, in order to define potential protocols for its use in patients.
“…Clinical detectors typically have a too thick entrance window to measure these low proton energies employed here. Nevertheless, there are alternatives to the appropriate extrapolation IC, such as radiochromic film dosimetry, 41 which, however, has large uncertainties, 23 as well as calibrated photostimulated image plates or solid state detectors CR39 42 …”
Section: Discussionmentioning
confidence: 99%
“…Clinical detectors typically have a too thick entrance window to measure these low proton energies employed here. Nevertheless, there are alternatives to the appropriate extrapolation IC, such as radiochromic film dosimetry, 41 which, however, has large uncertainties, 23 as well as calibrated photostimulated image plates or solid state detectors CR39. 42 A special application of this work was to find the ideal setup at a clinical proton accelerator for lowenergy experiments to perform cell irradiations comparable to the specifically presented case with LAP.…”
The adequate performance of radiobiological experiments using clinical proton beams typically requires substantial preparations to provide the appropriate setup for specific experiments. Providing radiobiologically interesting low-energy protons is a particular challenge, due to various physical effects that become more pronounced with larger absorber thickness and smaller proton energy. This work demonstrates the generation of decelerated low-energy protons from a clinical proton beam. Methods: Monte Carlo simulations of proton energy spectra were performed for energy absorbers with varying thicknesses to reduce the energy of the clinical proton beam down to the few-MeV level corresponding to μm-ranges. In this way, a setup with an optimum thickness of the absorber with a maximum efficiency of the proton fluence for the provisioning of low-energy protons is supposed to be found. For the specific applications of 2.5-3.3 MeV protons and 𝛼-particle range equivalent protons, the relative depth dose was measured and simulated together with the dose-averaged linear energy transfer (LETd) distribution.
Results:The resulting energy spectra from Monte Carlo simulations indicate an optimal absorber thickness for providing low-energy protons with maximum efficiency of proton fluence at an user-requested energy range for experiments. For instance, providing energies lower than 5 MeV, an energy spectrum with a relative total efficiency of 38.6% to the initial spectrum was obtained with the optimal setup. The measurements of the depth dose, compared to the Monte Carlo simulations, showed that the dosimetry of low-energy protons works and protons with high LETd down to the range of 𝛼-particles can be produced. Conclusions: This work provides a method for generating all clinically and radiobiologically relevant energies -especially down to the few-MeV levelat one clinical facility with pencil beam scanning. Thereby, it enables radiobiological experiments under environmentally uniform conditions.
“…Consequently, the Gafchromic EBT3 lm (ISP), a type of radiochromic lm, was applied for dosimetry of both proton, 125 I, and 106 Ru brachytherapy plaques. This lm has a symmetric structure which respectively includes 125 µm thickness Mate polyester over-layer, 28 µm thickness active layer, and 125 µm thickness Mate polyester substrate [5,33]. One of the main features of this Gafchromic lm is its very near tissue equivalency which allows the user to measure the absorbed dose with good accuracy.…”
Proton therapy and plaque-based brachytherapy are considered efficient radiotherapy modalities for intraocular tumor irradiation. The current study aims to measure and compare the dosimetric features of these methods through a film dosimetry approach inside an eyeball phantom. A 3D-printed PLA (polylactic acid)-based eyeball phantom was applied for phantom irradiation. For brachytherapy, COMS and CGD plaques respectively containing the 125I and 106Ru radioactive sources were employed. Proton irradiation was performed using the clinical beamline of the CNAO oncological hadron therapy center. PDD (percentage depth dose), transverse dose profile, 2D and 3D dose distribution, as well as DVH (dose volume histogram) data relevant to the tumor volume and surrounding healthy tissues were measured for applied treatment techniques using Gafchromic EBT3 film dosimetry approach and compared together. A more uniform dose distribution inside the tumor volume was found in the case of the proton beam concerning two other techniques. Furthermore, a proton beam can better spare healthy organs distributed around the tumor region. Besides, COMS plaque can lead to better clinical outcomes concerning CGD plaque. Viewpoint to the dose uniformity inside the target volume as well as sparing the healthy tissues, proton therapy would be the optimal choice. On the other hand, the photon beam can be preferred to the electron beam if proton therapy facilities are not available. Nevertheless, based on the importance of the healthy organ which should be spared, the COMS or CGD plaque can be selected for radiotherapy.
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