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Poster De Conférence Année : 2023

Parametric study of the impact of intracellular radionuclide distribution in Targeted Alpha Therapy, with multi-scale modeling

Résumé

Background: In the context of predicting biological effects in Targeted Alpha Therapy, nano/micro-dosimetry are essential because of the very heterogeneous dose deposition at cell level. The objective of this study is to evaluate theoretically the importance of radionuclide cell internalization on relevant dosimetric and biological endpoints. Material and Methods: The treatment with 211At of microtumors was simulated. The Monte Carlo CPOP code, based on Geant4, was used to generate realistic deformable 3D multi-cellular geometries, and was adapted to generate the radionuclide source distributions in various internalization cases (membrane, cytoplasm, cytoplasm + nucleus and nucleus only) and collect the physical outputs needed for the biophysical calculations. Specific energies in cell nuclei of ovarian cancer cell line OVCAR-3, have been calculated, in addition to therapeutic indexes like Tumor Control Probability (TCP), using the biophysical model NanOx. It uses both nano and microdosimetry to predict cell survivals. The impact of cell packing, tumor size, alphas energy and radionuclide daughter diffusion after fixation were studied. Results: In most cases, the radionuclide distribution had a low impact on specific energy at high radionuclide concentration (> 10 alpha particles per cell). However, for small tumors (30 μm radius) and low compaction spheroids (25% compaction), the specific energy increased up to 30% from membrane-to-nucleus distribution. When the number of alpha particles per cell were below 10, TCP could strongly depend on the radionuclide distributions, even for larger tumors, with, for example, factor up to 18 from membrane-to-nucleus distribution in a 95 μm tumor radius case. For an average 10% cell survival, RBEμ was found approximately equal to 6.9. Conclusions: Precise micro/nanometric modeling of the intracellular radionuclide distribution is needed for small micrometastases, low compaction spheroids, or, tumors with heterogeneous radionuclide concentration. Also, RBEμ has to be taken into account to observe these effects with TCP calculations. These results will be compared to experimental data, preliminary results will be presented.
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Dates et versions

hal-04305468 , version 1 (24-11-2023)

Identifiants

  • HAL Id : hal-04305468 , version 1

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Victor Levrague, Mario Alcocer-Avila, Sarah Otmani, Lydia Maigne, Etienne Testa, et al.. Parametric study of the impact of intracellular radionuclide distribution in Targeted Alpha Therapy, with multi-scale modeling. 17th International Congress for Radiation Research (ICRR), Aug 2023, Montréal, Canada. . ⟨hal-04305468⟩
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