Christos Bousis

Monte Carlo single-cell dosimetry of Auger-electron emitting radionuclides

A hybrid Monte Carlo transport scheme combining event-by-event and condensed-history simulation with a full account of energy-loss straggling was used to study the dosimetric characteristics of the Auger-emitting radionuclides 67Ga, 99mTc, 111In, 123I, 125I and 201Tl at the single-cell level. The influence of the intracellular localization of the Auger radionuclide upon cellular S-values, radial dose rate profiles and dose-volume-histograms (DVHs) was investigated. For the case where the radiopharmaceutical was either internalized into the cytoplasm or remained bound onto the cell surface (non-internalized), the dose to the cell nucleus was found to differ significantly from the MIRD values and other published data. In this case, the assumption of a homogeneous distribution throughout the cell is shown to significantly overestimate the nuclear dose. A dosimetric case study relevant to the radioimmunotherapy of single lymphoma B-cells with 125I and 123I is presented.

Subcellular S-factors for low-energy electrons: a comparison of Monte Carlo simulations and continuous-slowing-down calculations.

Purpose: To study the energy deposition by low-energy electrons in submicron tissue-equivalent targets by comparing two widely used methodologies, namely, the continuous-slowing-down-approximation (CSDA) convolution integral and the Monte Carlo (MC) simulation. Methods: An MC track-structure code that simulates collision-by-collision the complete slowing down process is used to calculate the energy deposition in spherical volumes of unit density water medium. Comparisons are made with calculations based on the CSDA convolution integral using both empirical and MC-based range-energy analytic formulae. Results: We present self-irradiation absorbed fractions and S-factors for monoenergetic electrons of initial energies from 0.1–10 keV distributed uniformly in spheres of 5, 10, 50, 100, 500, and 1000 nm radius. The MC and CSDA results were found, in some cases, to differ by a factor of 2 or more; differences generally increase with decreasing sphere size. Contrary to high energies, the uncertainties associated with the straight-ahead approximation implicit in the CSDA calculations are of the same order as those related to straggling and δ-ray effects. Conclusion: The use of the CSDA methodology may be unsuitable for the sub-micron scale where a more realistic description of electron transport becomes important.

A Monte Carlo study of absorbed dose distributions in both the vapor and liquid phases of water by intermediate energy electrons based on different condensed-history transport schemes.

Monte Carlo transport calculations of dose point kernels (DPKs) and depth dose profiles (DDPs) in both the vapor and liquid phases of water are presented for electrons with initial energy between 10 keV and 1 MeV. The results are obtained by the MC4 code using three different implementations of the condensed-history technique for inelastic collisions, namely the continuous slowing down approximation, the mixed-simulation with delta-ray transport and the addition of straggling distributions for soft collisions derived from accurate relativistic Born cross sections. In all schemes, elastic collisions are simulated individually based on single-scattering cross sections. Electron transport below 10 keV is performed in an event-by-event mode. Differences on inelastic interactions between the vapor and liquid phase are treated explicitly using our recently developed dielectric response function which is supplemented by relativistic corrections and the transverse contribution. On the whole, the interaction coefficients used agree to better than approximately 5% with NIST/ICRU values. It is shown that condensed phase effects in both DPKs and DDPs practically vanish above 100 keV. The effect of delta-rays, although decreases with energy, is sizeable leading to more diffused distributions, especially for DPKs. The addition of straggling for soft collisions is practically inconsequential above a few hundred keV. An extensive benchmarking with other condensed-history codes is provided.

A Monte Carlo study of cellular S-factors for 1 keV to 1 MeV electrons

A systematic study of cellular S-factors and absorbed fractions for monoenergetic electrons of initial energy from 1 keV to 1 MeV is presented. The calculations are based on our in-house Monte Carlo codes which have been developed to simulate electron transport up to a few MeV using both event-by-event and condensed-history techniques. An extensive comparison with the MIRD tabulations is presented for spherical volumes of 1-10 microm radius and various source-to-target combinations relevant to the intracellular localization of the emitted electrons. When the primary electron range is comparable to the sphere radius, we find significantly higher values from the MIRD, while with increasing electron energy the escape of delta-rays leads gradually to the opposite effect. The largest differences with the MIRD are found for geometries where the target region is at some distance from the source region (e.g. surface-to-nucleus or cytoplasm-to-nucleus). The sensitivity of the results to different transport approximations is examined. The grouping of inelastic collisions is found adequate as long as delta-rays are explicitly simulated, while the inclusion of straggling for soft collisions has a negligible effect.

Monte Carlo single-cell dosimetry of I-131, I-125 and I-123 for targeted radioimmunotherapy of B-cell lymphoma.

Abstract Purpose: To study the dosimetric characteristics of a non-internalizing and an internalizing monoclonal antibody (MAb) labeled with 131I, 125I or 123I, which targets a typical lymphoma B-cell. Materials and methods: Using our hybrid Monte Carlo (MC) code which combines detailed- and condensed-history electron track simulation we carry out transport calculations of Auger and beta electrons for different intracellular distributions of radioactivity. Results: Assuming permanent retention of the MAb in cells, 125I gave the highest absorbed dose and 123I the highest absorbed dose rate. Under the more realistic scenario of biologic excretion from the cells, 123I resulted in the highest absorbed dose and absorbed dose rate. Conclusion: The present dosimetric analysis shows that biological half-life, subcellular localization, and the proper account of low-energy electrons is critical in assessing the energy deposition inside the targeted cells from the three iodide radioisotopes examined. From a dosimetric point of view and under the present approximations 123I might be superior to the other two radioiodides in the treatment of microscopic disease in B-cell lymphoma patients.

Parallelization of a Monte Carlo particle transport simulation code

We have developed a high performance version of the Monte Carlo particle transport simulation code MC4. The original application code, developed in Visual Basic for Applications (VBA) for Microsoft Excel, was first rewritten in the C programming language for improving code portability. Several pseudo-random number generators have been also integrated and studied. The new MC4 version was then parallelized for shared and distributed-memory multiprocessor systems using the Message Passing Interface. Two parallel pseudo-random number generator libraries (SPRNG and DCMT) have been seamlessly integrated. The performance speedup of parallel MC4 has been studied on a variety of parallel computing architectures including an Intel Xeon server with 4 dual-core processors, a Sun cluster consisting of 16 nodes of 2 dual-core AMD Opteron processors and a 200 dual-processor HP cluster. For large problem size, which is limited only by the physical memory of the multiprocessor server, the speedup results are almost linear on all systems. We have validated the parallel implementation against the serial VBA and C implementations using the same random number generator. Our experimental results on the transport and energy loss of electrons in a water medium show that the serial and parallel codes are equivalent in accuracy. The present improvements allow for studying of higher particle energies with the use of more accurate physical models, and improve statistics as more particles tracks can be simulated in low response time.

Calculations of absorbed fractions in small water spheres for low-energy monoenergetic electrons and the Auger-emitting radionuclides123Ι and 125Ι

Abstract Purpose: To calculate the absorbed fraction (AF) of low energy electrons in small tissue-equivalent spherical volumes by Monte Carlo (MC) track structure simulation and assess the influence of phase (liquid water versus density-scaled water vapor) and of the continuous-slowing-down approximation (CSDA) used in semi-analytic calculations. Methods: An event-by-event MC code simulating the transport of electrons in both the vapor and liquid phase of water using appropriate electron-water interaction cross sections was used to quantify the energy deposition of low-energy electrons in spherical volumes. Semi-analytic calculations within the CSDA using a convolution integral of the Howell range-energy expressions are also presented for comparison. Results: The AF for spherical volumes of radii from 10–1000 nm are presented for monoenergetic electrons over the energy range 100–10,000 eV and the two Auger-emitting radionuclides 125I and 123I. The MC calculated AF for the liquid phase are found to be smaller than those of the (density scaled) gas phase by up to 10–20% for the monoenergetic electrons and 10% for the two Auger-emitters. Differences between the liquid-phase MC results and the semi-analytic CSDA calculations are up to ∼ 55% for the monoenergetic electrons and up to ∼ 35% for the two Auger-emitters. Conclusions: Condensed-phase effects in the inelastic interaction of low-energy electrons with water have a noticeable but relatively small impact on the AF for the energy range and target sizes examined. Depending on the electron energies, the semi-analytic approach may lead to sizeable errors for target sizes with linear dimensions below 1 micron.