Dataset Information

GATE/Geant4-based dosimetry for ex vivo in solution irradiation of blood with radionuclides.

ABSTRACT: To establish a dose-response relationship between radiation-induced DNA damage and the corresponding absorbed doses in blood irradiated with radionuclides in solution under ex vivo conditions, the absorbed dose coefficient for 1 ml for 1 h internal ex vivo irradiation of peripheral blood (d_Blood) must be determined. d_Blood is specific for each radionuclide, and it depends on the irradiation geometry. Therefore, the aim of this study is to use the Monte Carlo radiation transport code GATE/Geant4 to calculate the mean absorbed dose rates for ex vivo irradiation of blood with several radionuclides used in Nuclear Medicine.

Methods

The Monte Carlo simulation reproduces the irradiation geometry of a blood sample of 7 ml mixed with 1 ml of a water equivalent radioactive solution in an 8 ml vial. The simulation was performed for ten different radionuclides: ¹⁸F, ⁶⁸Ga, ⁹⁰Y, ^99mTc, ¹²³I, ¹²⁴I, ¹³¹I, ¹⁷⁷Lu, ²²³Ra, and ²²⁵Ac. Two sets of simulations for each radionuclide were performed with 1x10⁹ histories. The first set was simulated with a mass density of 1.0525 g/cm³ of the blood plus water mixture. The second set of simulations was performed with a mass density of 1 g/cm³ for comparison with previous studies.

Results

The values of d_Blood for ten radionuclides were calculated. The values range from 10.23 mGy∙ml∙MBq^-1 for ^99mTc to 15632.02 mGy∙ml∙MBq^-1 for ²²⁵Ac. The maximum relative change compared to previous studies was 13.0% for ¹²⁴I.

Conclusion

This study provides a comprehensive set of absorbed dose coefficients for 1 ml for 1 h internal ex vivo irradiation of peripheral blood in a special vial geometry and radionuclides typically used in Nuclear Medicine. Furthermore, the method proposed by this work can be easily adapted to a variety of internal irradiation conditions and serve as a reference for future studies.

SUBMITTER: Salas-Ramirez M

PROVIDER: S-EPMC10082371 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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GATE/Geant4-based dosimetry for ex vivo in solution irradiation of blood with radionuclides.

Salas-Ramirez Maikol M Lassmann Michael M Eberlein Uta U

Zeitschrift fur medizinische Physik 20220524 1

To establish a dose-response relationship between radiation-induced DNA damage and the corresponding absorbed doses in blood irradiated with radionuclides in solution under ex vivo conditions, the absorbed dose coefficient for 1 ml for 1 h internal ex vivo irradiation of peripheral blood (d<sub>Blood</sub>) must be determined. d<sub>Blood</sub> is specific for each radionuclide, and it depends on the irradiation geometry. Therefore, the aim of this study is to use the Monte Carlo radiation trans ...[more]

PMID: 35623943

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Project description:BackgroundThe aim of this study is to evaluate the induction of DNA damage by 45 radionuclides, including those used in medical applications and others relevant to radiation protection. The research focuses on understanding the differential effects of irradiating lymphocytes with beta/gamma- and alpha-emitting radionuclides using Monte Carlo simulations. A validated Monte Carlo simulation model was used to assess radiation-induced DNA damage in lymphocytes. The model integrates GATE for macroscopic radiation transport and Geant4-DNA for microscopic simulations at the cellular level. For the study, 45 radionuclides were selected and their S-values and DNA double-strand break (DSB) induction were investigated. For beta- and gamma-emitting radionuclides, DSBs per cell per mGy were quantified, while for alpha-emitters, alpha tracks per cell per mGy, DSBs per cell per mGy, and DSBs per micrometer of alpha track were calculated.ResultFor beta/gamma emitters, the lowest number of DSBs was observed with 125I at 0.006 ± 0.003 DSBs·cell⁻¹·mGy⁻¹, while 99mTc had the highest at approximately 0.015 ± 0.005 DSBs·cell⁻¹·mGy⁻¹. The S-value for lymphocyte nuclei ranked from 0.91 ± 0.14 mGy∙h⁻¹∙MBq⁻¹ (63Ni) and 1.06 ± 0.15 mGy∙h⁻¹∙MBq⁻¹ (125I) to 61.83 ± 1.17 mGy∙h⁻¹∙MBq⁻¹ (90Sr). For alpha-emitting radionuclides, 213Bi produced 0.0677 ± 0.0005 DSB·cell⁻¹·mGy⁻¹ while 232Th yielded 0.0914 ± 0.0004 DSB·cell⁻¹·mGy⁻¹. The DSB linear density for alpha tracks ranged from 7.4 ± 0.1 DSBs/µm for 252Cf to 16.8 ± 0.1 DSBs/µm for 232Th. The S-values for lymphocyte nuclei for alpha emitters varied, from 232Th (0.29 ± 0.21 Gy∙h⁻¹∙MBq⁻¹) to 227Th having the highest at 2.22 ± 0.16 Gy∙h⁻¹∙MBq⁻¹, due to cumulative energy deposition.ConclusionsDifferences were observed in DNA damage induced by beta/gamma- and alpha-emitting radionuclides. High-energy beta emitters induced DSBs similarly to gamma emitters, but with greater fluctuations in low-energy beta and gamma emitters due to heterogeneous energy deposition and varying interaction probabilities at the cellular level. This study highlights that long half-life alpha-emitting radionuclides may cause more extensive DNA damage due to their higher LET. This work provides a comprehensive S-values database for future experimental studies on radiation-induced DNA damage in lymphocytes.

Project description:PurposeThe dose core of a proton pencil beam (PB) is enveloped by a low dose area reaching several centimeters off the central axis and containing a considerable amount of the dose. Adequate modeling of the different components of the PB profile is, therefore, required for accurate dose calculation. In this study, we experimentally validated one electromagnetic and two nuclear scattering models in GATE/Geant4 for dose calculation of proton beams in the therapeutic energy window (62-252 MeV) with and without range shifter (RaShi).MethodsThe multiple Coulomb scattering (MCS) model was validated by lateral dose core profiles measured for five energies at up to four depths from beam plateau to Bragg peak region. Nuclear halo profiles of single PBs were evaluated for three (62.4, 148.2, and 252.7 MeV) and two (97.4 and 124.7 MeV) energies, without and with RaShi, respectively. The influence of the dose core and nuclear halo on field sizes varying from 2-20 cm was evaluated by means of output factors (OFs), namely frame factors (FFs) and field size factors (FSFs), to quantify the relative increase of dose when increasing the field size.ResultsThe relative increase in the dose core width in the simulations deviated negligibly from measurements for depths until 80% of the beam range, but was overestimated by up to 0.2 mm in σ toward the end of range for all energies. The dose halo region of the lateral dose profile agreed well with measurements in the open beam configuration, but was notably overestimated in the deepest measurement plane of the highest energy or when the beam passed through the RaShi. The root-mean-square deviations (RMSDs) between the simulated and the measured FSFs were less than 1% at all depths, but were higher in the second half of the beam range as compared to the first half or when traversing the RaShi. The deviations in one of the two tested hadron physics lists originated mostly in elastic scattering. The RMSDs could be reduced by approximately a factor of two by exchanging the default elastic scattering cross sections for protons.ConclusionsGATE/Geant4 agreed satisfyingly with most measured quantities. MCS was systematically overestimated toward the end of the beam range. Contributions from nuclear scattering were overestimated when the beam traversed the RaShi or at the depths close to the end of the beam range without RaShi. Both, field size effects and calculation uncertainties, increased when the beam traversed the RaShi. Measured field size effects were almost negligible for beams up to medium energy and were highest for the highest energy beam without RaShi, but vice versa when traversing the RaShi.

Project description:BackgroundPoor engraftment due to low cell doses restricts the usefulness of umbilical-cord-blood transplantation. We hypothesized that engraftment would be improved by transplanting cord blood that was expanded ex vivo with mesenchymal stromal cells.MethodsWe studied engraftment results in 31 adults with hematologic cancers who received transplants of 2 cord-blood units, 1 of which contained cord blood that was expanded ex vivo in cocultures with allogeneic mesenchymal stromal cells. The results in these patients were compared with those in 80 historical controls who received 2 units of unmanipulated cord blood.ResultsCoculture with mesenchymal stromal cells led to an expansion of total nucleated cells by a median factor of 12.2 and of CD34+ cells by a median factor of 30.1. With transplantation of 1 unit each of expanded and unmanipulated cord blood, patients received a median of 8.34×10(7) total nucleated cells per kilogram of body weight and 1.81×10(6) CD34+ cells per kilogram--doses higher than in our previous transplantations of 2 units of unmanipulated cord blood. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 15 days in the recipients of expanded cord blood, as compared with 24 days in controls who received unmanipulated cord blood only (P<0.001); the median time to platelet engraftment was 42 days and 49 days, respectively (P=0.03). On day 26, the cumulative incidence of neutrophil engraftment was 88% with expansion versus 53% without expansion (P<0.001); on day 60, the cumulative incidence of platelet engraftment was 71% and 31%, respectively (P<0.001).ConclusionsTransplantation of cord-blood cells expanded with mesenchymal stromal cells appeared to be safe and effective. Expanded cord blood in combination with unmanipulated cord blood significantly improved engraftment, as compared with unmanipulated cord blood only. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00498316.).

Dataset Information

GATE/Geant4-based dosimetry for ex vivo in solution irradiation of blood with radionuclides.

Methods

Results

Conclusion

Publications

GATE/Geant4-based dosimetry for ex vivo in solution irradiation of blood with radionuclides.

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