Feasibility study of using fall‐off gradients of early and late <scp>PET</scp> scans for proton range verification

Cho, Jongmin; Grogg, K. S.; Min, Chul Hee; Zhu, Xiaoying; Paganetti, Harald; Lee, Hyun Cheol; Fakhri, Georges El

doi:10.1002/mp.12191

Cited by 10 publications

(9 citation statements)

References 29 publications

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“…It is well-known that the 16 O(p,2p2n) 13 N reaction has a relatively low threshold energy (5.660 MeV) [ 22 ]. Therefore, by computing the gradient between early and late PET scans, one can extract the 13 N creation, which is discovered to be associated closely with the Bragg peak.…”

Section: Introductionmentioning

confidence: 99%

Proton range monitoring using 13N peak for proton therapy applications

Islam

Beni

et al. 2022

PLoS ONE

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The Monte Carlo method is employed in this study to simulate the proton irradiation of a water-gel phantom. Positron-emitting radionuclides such as 11C, 15O, and 13N are scored using the Particle and Heavy Ion Transport Code System Monte Carlo code package. Previously, it was reported that as a result of 16O(p,2p2n)13N nuclear reaction, whose threshold energy is relatively low (5.660 MeV), a 13N peak is formed near the actual Bragg peak. Considering the generated 13N peak, we obtain offset distance values between the 13N peak and the actual Bragg peak for various incident proton energies ranging from 45 to 250 MeV, with an energy interval of 5 MeV. The offset distances fluctuate between 1.0 and 2.0 mm. For example, the offset distances between the 13N peak and the Bragg peak are 2.0, 2.0, and 1.0 mm for incident proton energies of 80, 160, and 240 MeV, respectively. These slight fluctuations for different incident proton energies are due to the relatively stable energy-dependent cross-section data for the 16O(p,2p2n)13N nuclear reaction. Hence, we develop an open-source computer program that performs linear and non-linear interpolations of offset distance data against the incident proton energy, which further reduces the energy interval from 5 to 0.1 MeV. In addition, we perform spectral analysis to reconstruct the 13N Bragg peak, and the results are consistent with those predicted from Monte Carlo computations. Hence, the results are used to generate three-dimensional scatter plots of the 13N radionuclide distribution in the modeled phantom. The obtained results and the developed methodologies will facilitate future investigations into proton range monitoring for therapeutic applications.

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Section: Introductionmentioning

confidence: 99%

Proton range monitoring using 13N peak for proton therapy applications

Islam

Beni

et al. 2022

PLoS ONE

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“…Since β + -emitters originated by proton-induced reactions on human tissues, mainly 11 C and 15 O, have a relatively high production threshold (17.9 MeV for 12 C(p,X) 11 C and 14.3 MeV for 16 O(p,X) 15 O), they will not be formed in the proximity of the Bragg peak 10 limiting the applicability of PET imaging for proton beam range verification 11 . The use of 13 N produced from 16 O has been suggested as an alternative 12 due to the lower energy threshold (5.5 MeV), but its integrated cross-section at low energies may not be high enough 13 , and the 13 N specific activity decreases at a fast pace, due to its shorter half life and affected by biological washout processes.…”

Section: Introductionmentioning

confidence: 99%

In vivo production of fluorine-18 in a chicken egg tumor model of breast cancer for proton therapy range verification

España

Sánchez-Parcerisa

Bragado

et al. 2022

Sci Rep

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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.

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“…In proton therapy, high energy protons are used to deliver doses to tumors. As a result of the interaction between high energy protons with tissues, the tissue elements would be activated [ 12 ]. 1 H, 12 C and 16 O are the commonest elements found in body tissues, with 12 C and 16 O being able to produce 11 C and 15 O/ 13 N, respectively, which are positron emitting radioisotopes and in turn generate annihilation photons within the patient’s body.…”

Section: Introductionmentioning

confidence: 99%

“…Previously, Cho et al . [ 12 ] proposed to use the generated 13 N positron emitters for proton range verification due to its low energy threshold that peaks at around 12 MeV. In their previous study, water-like gel and tissue-like gel phantoms were irradiated and scanned using an in-room positron emission tomography (PET) system.…”

Section: Introductionmentioning

confidence: 99%

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Development of PHITS graphical user interface for simulation of positron emitting radioisotopes production in common biological materials during proton therapy

Beni

Islam

et al. 2022

Journal of Radiation Research

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The Monte Carlo (MC) method is a powerful tool for modeling nuclear radiation interaction with matter. A variety of MC software packages has been developed, especially for applications in radiation therapy. Most widely used MC packages require users to write their own input scripts for their systems, which can be a time consuming and error prone process and requires extensive user experience. In the present work, we have developed a graphical user interface (GUI) bundled with a custom-made 3D OpenGL visualizer for PHITS MC package. The current version focuses on modeling proton induced positron emitting radioisotopes, which in turn can be used for verification of proton ranges in proton therapy. The developed GUI program does not require extensive user experience. The present open-source program is distributed under GPLv3 license that allows users to freely download, modify, recompile and redistribute the program.

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Feasibility study of using fall‐off gradients of early and late PET scans for proton range verification

Cited by 10 publications

References 29 publications

Proton range monitoring using 13N peak for proton therapy applications

Proton range monitoring using 13N peak for proton therapy applications

In vivo production of fluorine-18 in a chicken egg tumor model of breast cancer for proton therapy range verification

Development of PHITS graphical user interface for simulation of positron emitting radioisotopes production in common biological materials during proton therapy

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