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BACKGROUND: Gold nanoparticles (GNPs) accumulated within tumor cells have been shown to sensitize tumors to radiotherapy. From a physics point of view, the observed GNP-mediated radiosensitization is due to various downstream effects of the secondary electron (SE) production from internalized GNPs such as GNP-mediated dose enhancement. Over the years, numerous computational investigations on GNP-mediated dose enhancement/radiosensitization have been conducted. However, such investigations have relied mostly on simple cellular geometry models and/or artificial GNP distributions. Thus, it is at least desirable, if not necessary, to conduct further investigations using cellular geometry models that properly reflect realistic cell morphology as well as internalized GNP distributions at the nanoscale. PURPOSE: The primary aim of this study was to develop a nanometer-resolution geometry model of a GNP-laden tumor cell for computational investigations of GNP-mediated dose enhancement/radiosensitization. The secondary aim was to demonstrate the utility of this model by quantifying GNP-induced SE tracks/dose distribution at sub-cellular levels for further validation of a nanoscopic dose point kernel (nDPK) method against full-fledged Geant4 Monte Carlo (MC) simulation. METHODS: A transmission electron microscopy (TEM) image of a single cell showing cytoplasm, cellular nucleus, and internalized GNPs in the cellular endosome was segmented into sub-cellular levels based on pixel value thresholding. A corresponding material density was allocated to each pixel, and, by adding a thickness, each pixel was transformed to a geometric voxel and imported as a Geant4-acceptable input geometry file. In Geant4-Penelope MC simulation, a clinical 6 MV photon beam was applied, vertically or horizontally to the cell surface, and energy deposition to the cellular nucleus and cytoplasm, due to SEs emitted by internalized GNPs, was scored. Next, nDPK calculations were performed by generating virtual electron tracks from each GNP voxel to all nucleus and cytoplasm voxels. Subsequently, another set of Geant4 simulation was performed with both Penelope and DNA physics models under the geometry closely mimicking in vitro cell irradiation with a clinical 6 MV photon beam, allowing for derivation of nDPK specific to this geometry and further comparison between Gean4 simulation and nDPK method. RESULTS: The Geant4-calculated SE tracks and associated energy depositions showed significant dependence on photon incidence angle. For perpendicular incidence, nDPK results showed good agreement (average percentage pixel-to-pixel difference of 0.4% for cytoplasm and 0.5% for nucleus) with Geant4 results, while, for parallel incidence, the agreement became worse (-1.7%-0.7% for cytoplasm and -5.5%-0.8% for nucleus). Under the 6 MV cell irradiation geometry, nDPK results showed reasonable agreement (pixel-to-pixel Pearson's product moment correlation coefficient of 0.91 for cytoplasm and 0.98 for nucleus) with Geant4 results. CONCLUSIONS: The currently developed TEM-based model of a GNP-laden cell offers unprecedented details of realistic intracellular GNP distributions for nanoscopic computational investigations of GNP-mediated dose enhancement/radiosensitization. A benchmarking study performed with this model showed reasonable agreement between Geant4- and nDPK-calculated intracellular dose deposition by SEs emitted from internalized GNPs, especially under perpendicular incidence - a popular cell irradiation geometry and when the Geant4-Penelope physics model was used.

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PURPOSE: Absorbed dose calculation by kernel convolution requires the prior determination of dose point kernels (DPK). This study reports on the design, implementation, and test of a multi-target regressor approach to generate the DPKs for monoenergetic sources and a model to obtain DPKs for beta emitters. METHODS: DPK for monoenergetic electron sources were calculated using the FLUKA Monte Carlo (MC) code for many materials of clinical interest and initial energies ranging from 10 to 3000 keV. Regressor Chains (RC) with three different coefficients regularization/shrinkage models were used as base regressors. Electron monoenergetic scaled DPKs (sDPKs) were used to assess the corresponding sDPKs for beta emitters typically used in nuclear medicine, which were compared against reference published data. Finally, the beta emitters sDPK were applied to a patient-specific case calculating the Voxel Dose Kernel (VDK) for a hepatic radioembolization treatment with [Formula: see text]Y. RESULTS: The three trained machine learning models demonstrated a promising capacity to predict the sDPK for both monoenergetic emissions and beta emitters of clinical interest attaining differences lower than [Formula: see text] in the mean average percentage error (MAPE) as compared with previous studies. Furthermore, differences lower than [Formula: see text] were obtained for the absorbed dose in patient-specific dosimetry comparing against full stochastic MC calculations. CONCLUSION: An ML model was developed to assess dosimetry calculations in nuclear medicine. The implemented approach has shown the capacity to accurately predict the sDPK for monoenergetic beta sources in a wide range of energy in different materials. The ML model to calculate the sDPK for beta-emitting radionuclides allowed to obtain VDK useful to achieve reliable patient-specific absorbed dose distributions required short computation times.

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PURPOSE: In nuclear medicine, Dose Point Kernels (DPKs), representing the energy deposited all around a point isotropic source, are extensively used for dosimetry and are usually obtained by Monte Carlo (MC) simulations. For beta-decaying nuclides, DPK is usually estimated neglecting Internal Bremsstrahlung (IB) emission, a process always accompanying the beta decay and consisting in the emission of photons having a continuous spectral distribution. This work aims to study the significance of IB emission for DPK estimation in the case of 32P and provide DPK values corrected for the IB photon contribution. METHODS: DPK, in terms of the scaled absorbed dose fraction, F(R/X90), was first estimated by GAMOS MC simulation using the standard beta decay spectrum of 32P, Fß(R/X90). Subsequently, an additional source term accounting for IB photons and their spectral distribution was defined and used for a further MC simulation, thus evaluating the contribution of IB emission to DPK values, Fß+IB(R/X90). The relative percent difference, δ, between the DPKs obtained by the two approaches, Fß+IB vs. Fß, was studied as a function of the radial distance, R. RESULTS: As far as the energy deposition is mainly due to the beta particles, IB photons does not significantly contribute to DPK; conversely, for larger R, Fß+IB values are higher by 30-40% than Fß. CONCLUSIONS: The inclusion of IB emission in the MC simulations for DPK estimations is recommended, as well as the use of the DPK values corrected for IB photons, here provided.

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BACKGROUND: Internal dosimetry has an increasing role in the planning and verification of nuclear medicine therapies with radiopharmaceuticals. Dose Point Kernels (DPKs), quantifying the energy deposition all around a point source, in a homogenous medium, are extensively used for 3D dosimetry and nowadays are mostly evaluated by Monte Carlo (MC) simulation. To our knowledge, DPK for beta emitters is estimated neglecting the continuous photon emission due to the Internal Bremsstrahlung (IB), whose contribution to the absorbed dose can be relevant beyond the maximum range of betas, as evidenced in recent works. PURPOSE: Aim of this study was to investigate and quantify, by means of MC simulations, the contribution of IB photons to DPK calculated for 90 Y and provide the updated 90 Y DPK. METHODS: The overall radiation due to the decay of a 90 Y point source, placed at the centre of concentric water shells of increasing radii from 0.02 cm to 20 cm, was simulated with GAMOS, including the IB source term whose spectral distribution was described by an analytical model. Energy deposition was scored in the shells as a function of the distance from the source, R, and DPK was estimated in terms of the scaled absorbed dose fraction, F(R/X90 ), where X90 is the range within which the beta particles deposit 90% of their energy. RESULTS: A comparison between the two simulated absorbed dose distributions, calculated with or without IB, clearly shows that the latter (incomplete) choice is consistent with the findings of other Authors and systematically underestimates the absorbed dose imparted to the tissue. 90 Y DPK values currently used are underestimated by 20%-34% for R>2X90 . CONCLUSIONS: The revised values provided in this work suggest that the inclusion of IB emission in DPK evaluations is advisable for pure beta emitters.

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BACKGROUND: Due to the importance of choosing the applicable dosimetry method in radionuclide therapy, the present study was conducted to investigate the efficiency of the implementation of Dose Point Kernel (DPK) for dose optimization of 177Lu/90Y Cocktail Radionuclides in internal Dosimetry. METHODS: In this study, simulations and calculations of DPK were performed using the GATE/GEANT4 Monte Carlo code. For specific liver dosimetry, the NCAT phantom and convolution algorithm-based Fast Fourier Transform method was used by MATLAB software. RESULTS: The self-dose of 177Lu and 90Y radionuclides in the liver of NCAT phantom were 1.1708E-13, and 4.8420E-11 (Gy/Bq), respectively, and the cross-dose of 177Lu and 90Y radionuclides out of the liver of NCAT phantom were 2.03615E-16, and 0.8422E-13 (Gy/Bq) respectively. Overall results showed that with an increase the value of 90Y with quarter steps in a cocktail, the amount of the self-dose increase 1.5, 6, and 29 times respectively, and with an increase the value of 177Lu in quarter step in a cocktail, the amount of the cross dose decrease 3, 15 and 68 percent respectively. CONCLUSION: Generally, the present results indicate that the calculated DPK functions of 177Lu and 90Y cocktails can play an important role in choosing the best combination of radionuclide to optimize treatment planning in cocktail radionuclide therapy.

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BACKGROUND: Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images. METHODS: Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new "Multi-tumor Partition Model" (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest. RESULTS: Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed. CONCLUSIONS: Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

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The use of radiolabeled molecules for tumor targeting constitutes a remarkable technique for the treatment of systemic malignancies. An accurate patient-specific dosimetry in nuclear medicine procedures should be a relevant pre-requisite in order to achieve the required lethal damage to tumor cells while maintaining possible side-effects to normal tissues at tolerable levels. It is desired to assess in vivo the radiopharmaceutical distribution for further estimation of absorbed dose released to target and involved organs. In this context, it was developed a computational toolkit, called DOSIS, in order to perform patient-specific dosimetry based on personalized patient anatomy and biodistribution of radionuclides both obtained by currently available dual PET/CT or SPECT/CT facilities. This work is focused on comparing 3D dose distributions obtained by DOSIS performing full stochastic Monte Carlo simulations versus analogue distributions obtained with analytical approaches like dose point kernel convolution and local energy deposition, when considering non-homogeneous activity or density distributions at different scales. Mathematical virtual phantoms were created for this study in order to compare results with other calculation methods. Some of the beta-emitters radionuclides commonly used for therapy (90Y, 131I, 177Lu) were investigated, and emissions of beta-particles, conversion electrons, gamma radiation, and characteristic X-rays were considered. DOSIS implements a novel code devoted to managing radiation transport simulation by means of PENELOPE Monte Carlo general-purpose routines on voxelized geometries defined by 3D mass and activity distributions. Both distributions can be defined through patients-specific images, or pre-defined virtual phantoms. Results preliminary confirmed DOSIS as a reliable and accurate toolkit for personalized internal dosimetry along with highlighting advantages/drawbacks of the different calculation schemes proposed.

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PURPOSE: The unique decay properties of copper-64 (64 Cu) has made it a radionuclide of interest in theragnostic applications of nuclear medicine. This study aims to calculate the dose point kernels (DPKs) of 64 Cu in various media with PENELOPE Monte Carlo code. METHODS: Monte Carlo simulations were performed using PENELOPE code (version 2014). To calculate DPKs, the simulation comprised an isotropic point radiation source positioned at the origin of a spherical object of radius 50 cm. The absorbed dose along the radial direction outwards from the point source were scored with a resolution of 20 µm. Validations were firstly performed by calculating the DPKs of monoenergetic electrons and photons in water and the results were compared against the literature values. The continuous energy spectra of the beta minus and positron emissions from 64 Cu were numerically modeled and used as inputs to the simulation. DPKs of 64 Cu were calculated in water, soft tissue, lung tissue, and cortical bone, including all emissions types. RESULTS: The simulations have been successfully validated against literature values. The largest deviations have been observed with 10 keV monoenergetic electrons with the average and maximum dose difference of -1.01% and -10.56%. The modeled energy spectra closely compared with the average energies from Brookhaven Laboratory National Nuclear Data Centre and the combined spectral shapes from the RAdiation Dose Assessment Resource (RADAR). The DPKs of 64 Cu demonstrated different radial dose deposition in different media owing to the different physical density and effective atomic number. CONCLUSIONS: The DPKs of 64 Cu have been calculated with Monte Carlo simulations in four different media. They will be useful to study the dosimetric properties of 64 Cu-labeled radiopharmaceuticals and perform therapeutic dose planning.

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We assessed the accuracy of mono-energetic electron and beta-emitting isotope dose-point kernels (DPKs) calculated using the particle and heavy ion transport code system (PHITS) for patient-specific dosimetry in targeted radionuclide treatment (TRT) and compared our data with published data. All mono-energetic and beta-emitting isotope DPKs calculated using PHITS, both in water and compact bone, were in good agreement with those in literature using other MC codes. PHITS provided reliable mono-energetic electron and beta-emitting isotope scaled DPKs for patient-specific dosimetry.

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PURPOSE: The aim of this work is to evaluate the application of tissue-specific dose kernels instead of water dose kernels to improve the accuracy of patient-specific dosimetry by taking tissue heterogeneities into consideration. MATERIALS AND METHODS: Tissue-specific dose point kernels (DPKs) and dose voxel kernels (DVKs) for yttrium-90 (90Y), lutetium-177 (177Lu), and phosphorus-32 (32P) are calculated using the Monte Carlo (MC) simulation code GATE (version 7). The calculated DPKs for bone, lung, adipose, breast, heart, intestine, kidney, liver, and spleen are compared with those of water. The dose distribution in normal and tumorous tissues in lung, liver, and bone of a Zubal phantom is calculated using tissue-specific DVKs instead of those of water in conventional methods. For a tumor defined in a heterogeneous region in the Zubal phantom, the absorbed dose is calculated using a proposed algorithm, taking tissue heterogeneity into account. The algorithm is validated against full MC simulations. RESULTS: The simulation results indicate that the highest differences between water and other tissue DPKs occur in bone for 90Y (12.2% ± 0.6%), 32P (18.8% ± 1.3%), and 177Lu (16.9% ± 1.3%). The second highest discrepancy corresponds to the lung for 90Y (6.3% ± 0.2%), 32P (8.9% ± 0.4%), and 177Lu (7.7% ± 0.3%). For 90Y, the mean absorbed dose in tumorous and normal tissues is calculated using tissue-specific DVKs in lung, liver, and bone. The results are compared with doses calculated considering the Zubal phantom water equivalent and the relative differences are 4.50%, 0.73%, and 12.23%, respectively. For the tumor in the heterogeneous region of the Zubal phantom that includes lung, liver, and bone, the relative difference between mean calculated dose in tumorous and normal tissues based on the proposed algorithm and the values obtained from full MC dosimetry is 5.18%. CONCLUSIONS: A novel technique is proposed considering tissue-specific dose kernels in the dose calculation algorithm. This algorithm potentially enables patient-specific dosimetry and improves estimation of the average absorbed dose of 90Y in a tumor located in lung, bone, and soft tissue interface by 6.98% compared with the conventional methods.

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PURPOSE: Experimental and theoretical dosimetry of the RIC-100 phosphorus-32 brachytherapy source is presented for implant geometries that may occur in an intraoperative setting during treatment of localized spinal tumors with temporary superficial radiation. Dose variation, due to source shape and size, is evaluated, and nonideal implant conditions are simulated. METHODS AND MATERIALS: Calibration, depth dose, and dose profiles were evaluated for several implant geometries and source sizes. Experimental measurements were performed using EBT3 gafchromic film. Theoretical calculations were performed using dose point kernel (DPK) formalism, which simulates isotropic, monoenergetic point sources distributed uniformly throughout the source and emitting electrons radially outward. RESULTS: Calibration and depth dose for RIC-100 are independent of source size for diameters >1 cm. Sources should be ordered with physical dimensions ∼0.2 cm larger than the target size, in all dimensions, to deliver >90% prescription dose to target edges. Relative dose profile shape is approximately constant as a function of target depth. Air gaps between the source and target cause narrower dose profile widths and shallower depth dose in the therapeutic range. DPK for RIC-100 agrees with published P-32 kernels, and DPK calculations agree with measurement (within 5%) for many depths and geometries. CONCLUSIONS: Intraoperative placement and measurement dosimetry of RIC-100 require careful setup due to steep dose gradients. Physical source dimensions should be chosen carefully based on treatment site dimensions, and air gaps between source and target should be minimized, to prevent underdosing the target in the lateral extent. Radiological scaling should be used to calculate expected dose when nonwater materials are used in experimental measurements, such as calibration or depth dose.

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Modeling the radio-induced effects in biological medium still requires accurate physics models to describe the interactions induced by all the charged particles present in the irradiated medium in detail. These interactions include inelastic as well as elastic processes. To check the accuracy of the very low energy models recently implemented into the GEANT4 toolkit for modeling the electron slowing-down in liquid water, the simulation of electron dose point kernels remains the preferential test. In this context, we here report normalized radial dose profiles, for mono-energetic point sources, computed in liquid water by using the very low energy "GEANT4-DNA" physics processes available in the GEANT4 toolkit. In the present study, we report an extensive intra-comparison of profiles obtained by a large selection of existing and well-documented Monte-Carlo codes, namely, EGSnrc, PENELOPE, CPA100, FLUKA and MCNPX.