Multiphysics Modelling of Background Dose by Systemic Targeted Alpha Therapy.

Area of Science:

• Medical Physics
• Radiotherapy
• Computational Biology

Background:

• Nontargeted alpha-immunoconjugates (AIC) in targeted alpha therapy (TAT) can spread via blood and lymphatic systems.
• Understanding AIC transport is vital for optimizing TAT efficacy and minimizing off-target radiation exposure.

Purpose of the Study:

• To establish a multiphysics simulation strategy for modeling AIC delivery in blood vessels.
• To investigate the transient drug delivery process and background radiation dose to cells.
• To determine the transient toxicity of AIC to targeted cell DNA.

Main Methods:

• A coupled Geant4 Monte Carlo microdosimetry and computational fluid dynamics model was developed.
• Mesoscale numerical simulations were performed in a 2D capillary model.
• The model investigated transient AIC delivery, background dose, and cellular toxicity.

Main Results:

• Multiphysics simulation is essential for enhancing the accuracy of targeted alpha therapy simulations.
• The study successfully modeled AIC delivery dynamics at a mesoscale level.
• Transient toxicity to targeted cell DNA was assessed.

Conclusions:

• A novel solution strategy for mesoscale modeling of AIC delivery in blood vessels was established.
• This work provides a comprehensive multiphysics simulation approach for understanding targeted alpha therapy.
• The findings are crucial for advancing the accuracy and effectiveness of targeted alpha therapy treatments.