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PET monitoring of cancer therapy with He-3 and C-12 beams: a study with the GEANT4 toolkit

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 Added by Igor Pshenichnov
 Publication date 2007
  fields Physics
and research's language is English




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We study the spatial distributions of $beta^+$-activity produced by therapeutic beams of $^3$He and $^{12}$C ions in various tissue-like materials. The calculations were performed within a Monte Carlo model for Heavy-Ion Therapy (MCHIT) based on the GEANT4 toolkit. The contributions from $^{10,11}$C, $^{13}$N, $^{14,15}$O, $^{17,18}$F and $^{30}$P positron-emitting nuclei were calculated and compared with experimental data obtained during and after irradiation. Positron emitting nuclei are created by $^{12}$C beam in fragmentation reactions of projectile and target nuclei. This leads to a $beta^+$-activity profile characterised by a noticeable peak located close to the Bragg peak in the corresponding depth-dose distribution. On the contrary, as the most of positron-emitting nuclei are produced by $^3$He beam in target fragmentation reactions, the calculated total $beta^+$-activity during or soon after the irradiation period is evenly distributed within the projectile range. However, we predict also the presence of $^{13}$N, $^{14}$O, $^{17,18}$F created in charge-transfer reactions by low-energy $^3$He ions close to the end of their range in several tissue-like media. The time evolution of $beta^+$-activity profiles was investigated for both kinds of beams. Due to the production of $^{18}$F nuclide the $beta^+$-activity profile measured 2 or 3 hours after irradiation with $^{3}$He ions will have a distinct peak correlated with the maximum of depth-dose distribution. We found certain advantages of low-energy $^{3}$He beams over low-energy proton beams for reliable PET monitoring during particle therapy of shallow located tumours. In this case the distal edge of $beta^+$-activity distribution from $^{17}$F nuclei clearly marks the range of $^{3}$He in tissues.



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We model the responses of Tissue-Equivalent Proportional Counters (TEPC) to radiation fields of therapeutic C-12 beams in a water phantom and to quasi-monoenergetic neutrons in a PMMA phantom. Simulations are performed with the Monte Carlo model for Heavy Ion Therapy (MCHIT) based on the Geant4 toolkit. The shapes of the calculated lineal energy spectra agree well with measurements in both cases. The influence of fragmentation reactions on the TEPC response to a narrow pencil-like beam with its width smaller than the TEPC diameter is investigated by Monte Carlo modeling. It is found that total lineal energy spectra are not very sensitive to the choice of the nuclear fragmentation model used. The calculated frequency-mean lineal energy y_f differs from the data on the axis of a therapeutic beam by less than 10% and by 10-20% at other TEPC positions. The validation of MCHIT with neutron beams gives us confidence in estimating the contributions to lineal energy spectra due to secondary neutrons produced in water by C-12 nuclei. As found, the neutron contribution at 10 cm distance from the beam axis amounts to ~ 50% close the entrance to the phantom and decreases to ~ 25% at the depth of the Bragg peak and beyond it. The presented results can help in evaluating biological out-of-field doses in carbon-ion therapy.
Beams of $^{4}$He and $^{16}$O nuclei are considered for ion-beam cancer therapy as alternative options to protons and $^{12}$C nuclei. Spread-out Bragg peak (SOBP) distributions of physical dose and relative biological effectiveness for 10% survival are calculated by means of our Geant4-based Monte Carlo model for Heavy Ion Therapy (MCHIT) and the modified microdosimetric kinetic model. The depth distributions of cell survival fractions are calculated for $^{1}$H, $^{4}$He, $^{12}$C and $^{16}$O for tissues with normal (HSG cells), low and high radiosensitivity. In each case the cell survival fractions were compared separately for the target volume, behind and in front of it. In the case of normal radiosensitivity $^{4}$He and $^{12}$C better spare tissues in the entrance channel compared to protons and $^{16}$O. The cell survival fractions calculated, respectively, for the entrance channel and target volume are similar for $^{4}$He and $^{12}$C. When it is important to spare healthy tissues located after the distal edge of the SOBP plateau, $^{4}$He can be recommended due to reduced nuclear fragmentation of these projectiles. No definite advantages of $^{16}$O with respect to $^{12}$C were found, with the except of an enhanced impact of these heavier projectiles on radioresistant tumors.
Background: Treatment verification with PET imaging in charged particle therapy is conventionally done by comparing measurements of spatial distributions with Monte Carlo (MC) predictions. However, decay curves can provide additional independent information about the treatment and the irradiated tissue. Most studies performed so far focus on long time intervals. Here we investigate the reliability of MC predictions of space and time (decay rate) profiles shortly after irradiation, and we show how the decay rates can give an indication about the elements of which the phantom is made up. Methods and Materials: Various phantoms were irradiated in clinical and near-clinical conditions at the Cyclotron Centre of the Bronowice proton therapy centre. PET data were acquired with a planar 16x16 cm$^2$ PET system. MC simulations of particle interactions and photon propagation in the phantoms were performed using the FLUKA code. The analysis included a comparison between experimental data and MC simulations of space and time profiles, as well as a fitting procedure to obtain the various isotope contributions in the phantoms. Results and conclusions: There was a good agreement between data and MC predictions in 1-dimensional space and decay rate distributions. The fractions of $^{11}$C, $^{15}$O and $^{10}$C that were obtained by fitting the decay rates with multiple simple exponentials generally agreed well with the MC expectations. We found a small excess of $^{10}$C in data compared to what was predicted in MC, which was clear especially in the PE phantom.
A Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT) is used to study radiation fields of H-1, He-4, Li-7 and C-12 beams with similar ranges (~160-180 mm) in water. Microdosimetry spectra are simulated for wall-less and walled Tissue Equivalent Proportional Counters (TEPCs) placed outside or inside a phantom, as in experiments performed, respectively, at NIRS, Japan and GSI, Germany. The impact of fragmentation reactions on microdosimetry spectra is investigated for He-4, Li-7 and C-12, and contributions from nuclear fragments of different charge are evaluated for various TEPC positions in the phantom. The microdosimetry spectra measured on the beam axis are well described by MCHIT, in particular, in the vicinity of the Bragg peak. However, the simulated spectra for the walled TEPC far from the beam axis are underestimated. Relative Biological Effectiveness (RBE) of the considered beams is estimated using a modified microdosimetric-kinetic model. Calculations show a similar rise of the RBE up to 2.2-2.9 close to the Bragg peak for helium, lithium and carbon beams compared to the modest values of 1-1.2 at the plateau region. Our results suggest that helium and lithium beams are also promising options for cancer therapy.
Charged particle beams are used in Particle Therapy (PT) to treat oncological patients due to their selective dose deposition in tissues and to their high biological effect in killing cancer cells with respect to photons and electrons used in conventional radiotherapy. Nowadays, protons and carbon ions are used in PT clinical routine but, recently, the interest on the potential application of helium and oxygen beams is growing due to their reduced multiple scattering inside the body and increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands for online dose monitoring techniques, crucial to improve the quality assurance of treatments. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Prompt photons are produced by nuclear de-excitation processes and, at present, different dose monitoring and beam range verification techniques based on the prompt {gamma} detection have been proposed. It is hence of importance to perform the {gamma} yield measurement in therapeutical-like conditions. In this paper we report the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a PMMA target. The measurements were performed at the Heidelberg Ion-beam Therapy center (HIT) with beams of different energies. A LYSO scintillator has been used as photon detector. The obtained {gamma} yields for $^{12}$C ion beams are compared with results from literature, while no other results from $^{4}$He and $^{16}$O beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-{gamma} based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.
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