Ponente
Descripción
Radiopharmaceutical therapy (RPT) is a novel modality of oncology treatments that uses radiolabeled agents affine to biomolecules overexpressed in tumor cell environments. RPT has the potential to improve outcomes for oncologic patients with distant metastases compared to external radiation therapies. This is due to its ability to target specifically cancerous cells while sparing healthy cells. In vitro radiopharmaceutical experiments are crucial because they provide a controlled environment to examine the interactions between radiolabeled compounds and biological systems.
Our research group has developed a computational extension to the TOPAS Monte Carlo toolkit to model irradiation experiments involving in vitro cell adherent layers. We have built a new geometry for monolayer cells, assumed as identical cylinders in a regular layout. Also, our tool simulates the time evolution of radioactive decay, particularizing results in time steps for the entire decay chain of a given radionuclide. Thus, the extension recreates the temporal evolution of irradiation conditions by specifying the radionuclide, the initial activity, the number of time steps to be simulated, and the duration of the experiment.
Typically, in vitro experiments exploring the effects of RPT have three separate processes of relevance: the injection of the radionuclide into the culture medium, the binding process of the radiopharmaceutical to a receptor on cell membranes, and the internalization process into the cell cytoplasm. Our simulations are correspondingly divided into three static stages: (i) when the radiopharmaceuticals are diluted in the medium, for which we consider a uniform distribution of sources; (ii) a second stage when the culture is washed out and the medium replaced but no internalization has taken place yet, for which radioactive emissions happen from cell membranes; and (iii) a final stage with only internalized radioactivity. With this approach, the simulation provides dose and dose rate evolution along the experiment.
Radiopharmaceutical in vitro experiments with pancreatic ductal adenocarcinoma (PDAC) cell lines, published by Kasten et al. [1] have been recreated. In their work, they set the duration of the first stage enabling binding processes to 2 hours, the second stage, which involves the internalization process to 48 h, and during the third stage, the cell culture was irradiating with sources along the cytoplasm for 12 days. The curve of the dose rate averaged over all cell nuclei is shown in the figure attached.
[1] Kasten BB et al. “212Pb-labeled B7-H3-targeting antibody for pancreatic cancer therapy in mouse models”, Nucl Med Biol. 58: 67-73 (2018).
