Ponente
Descripción
Background and aims
Radiopharmaceutical therapy (RPT) is a novel modality of oncology treatments which uses radiolabeled agents affine to biomolecules overexpressed in tumor cell environments. Alpha particle emitters are key in RPT by precisely targeting cancer cells while minimizing impact on healthy tissue, thanks to their limited range and localized energy delivery. In addition, this kind of treatment can be combined with protons, and heavy ions external radiotherapy to treat metastasis patient. Consequently, comprehending the distribution of doses with in vitro experiments is essential for advancing in the design of these treatments.
In general, in vitro experiments involve three distinct and relevant processes occurring simultaneously: the injection of the radionuclide into the culture medium, the binding of the radiopharmaceutical to receptors on cell membranes, and the internalization process within the cell cytoplasm. We have developed a TOPAS Monte Carlo to model the in vitro radiopharmaceutical experiments.
Methods
In our simulations, we have established a dynamic equilibrium involving the three processes mentioned earlier. The entire decay chain is simulated, and decays take place throughout the culture medium, cell membranes, and cytoplasm, considering the dynamic binding and internalization processes, which are influenced by the temporal evolution of the experiment. The computational tool presents two newly developed geometries: a two-dimensional monolayer of cells and a three-dimensional tumor sphere culture. To replicate irradiation conditions, the simulation specifies the radionuclide, initial activity, and experiment duration for both geometric configurations.
Results
Using the tool developed, a radiopharmaceutical in vitro experiment published by Kasten et al. [Nucl Med Biol. 58, 2018] with PDAC cell and the alpha emitter 212Pb has been recreated. Dose and dose rate evolution along the experiment have been scored for each cell individually.
Conclusions
The results obtained provide insights into how alpha particles induce damage. The findings suggest that the accumulated dose over an extended period is not the primary indicator, but it is the dose administered in short time intervals that truly determines the probability of cell death. These results carry significant implications for the design and advancement of therapies involving protons, alphas, and heavy ions.
