Tao Xu1, Yu Liu2, Tong Liu3, Gang Li4, Nusret Aydemir5. 1. Research Scientist, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada. Electronic address: tao.xu@cnl.ca. 2. Assistant Professor, Department of Electrical and Computer Engineering, Clarkson University, Potsdam, NY, USA. 3. Research Scientist, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada. 4. Applied Physicist, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada. 5. Thermalhydraulics Specialist, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada.
Abstract
INTRODUCTION: Nontargeted molecules of alpha-immunoconjugate (AIC) intravenously injected in clinical trials of targeted alpha therapy (TAT) could be transported by convection and diffusion along with blood or lymphatic circulation. MATERIALS AND METHODS: A coupled model based on the Geant4 Monte Carlo microdosimetry technique and computational fluid dynamics was established. The transient drug delivery process and background dose to the cells along the pathway were investigated using the model. A mesoscale numerical simulation in a simple 2D capillary was performed to determine the transient toxicity of the alpha-immunoconjugate to the DNA of a targeted cell. RESULTS: The simulation results indicate that the multiphysics simulation is essential to improve the accuracy of TAT simulation. CONCLUSION: In this work, a solution strategy for modelling AIC delivery in a blood vessel at a mesoscale level has been established. This work is the first to model different phenomena through the multiphysics simulation to investigate the whole picture of TAT.
INTRODUCTION: Nontargeted molecules of alpha-immunoconjugate (AIC) intravenously injected in clinical trials of targeted alpha therapy (TAT) could be transported by convection and diffusion along with blood or lymphatic circulation. MATERIALS AND METHODS: A coupled model based on the Geant4 Monte Carlo microdosimetry technique and computational fluid dynamics was established. The transient drug delivery process and background dose to the cells along the pathway were investigated using the model. A mesoscale numerical simulation in a simple 2D capillary was performed to determine the transient toxicity of the alpha-immunoconjugate to the DNA of a targeted cell. RESULTS: The simulation results indicate that the multiphysics simulation is essential to improve the accuracy of TAT simulation. CONCLUSION: In this work, a solution strategy for modelling AIC delivery in a blood vessel at a mesoscale level has been established. This work is the first to model different phenomena through the multiphysics simulation to investigate the whole picture of TAT.
Keywords:
Monte Carlo (MC); alpha-immunoconjugate (AIC); computational fluid dynamics (CFD); linear energy transfer (LET); targeted alpha therapy (TAT)