Improving dosage and timing of radiopharmaceutical therapies using computational modeling of tumor and radioligand dynamics
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Purpose
Radiopharmaceutical therapies (RPTs) are showing significant value in targeting various forms of cancer; meanwhile, as an emerging paradigm there is significant room for optimization of RPTs. We developed a computational model towards improving therapeutic strategies via modification of dosage and timing of RPT injections.
Methods
Our model simulates tumor growth, the pharmacokinetics of RPTs, and the radiobiological impact of radionuclide decay through energy deposition on tumor tissue. Specifically, we use the Hybrid Automata Library (HAL) to simulate tissue containing a heterogeneous tumor and its vasculature, along with oxygen and radiopharmaceutical concentration. Therapeutic interventions are modeled using a multiscale approach that connects whole-body compartmental modeling of radiopharmaceutical concentrations to the linear-quadratic survival model for tumor cells. We evaluated several treatment schedules applied to tumors with different conditions resulting in insights on how to improve RPTs.
Results
Tumors with varying vascular densities responded differently to identical therapeutic regimens. We also found that the timing and frequency of therapeutic interventions played important roles in the effectiveness of RPTs. Overall, we demonstrated that a one-size-fits-all approach is inadequate for achieving optimal therapies.
Conclusions
Our model provided insights for improving treatment schedules that highlight the potential for personalized approaches to achieve better outcomes. The code for the model is publicly available on GitHub: github.com/Elahe-hmh/HAL_RPT
