Development of an integrated multi-physics model to calculate the distributed absorbed dose for patients under Targeted Alpha Therapy

Abstract

To effectively evaluate internal dosimetry and predict biological effects of Targeted Alpha Therapy (TAT) in pre-clinical studies, dosimetry calculations based on the micro-level distributions of emitters are essential. However, the micro level distribution of emitters cannot be measured in patients with current technology. A new multi-physics toolset that is capable of predicting the micro level distribution of Ac-225 after its administration to a patient is currently under development at CNL (Canadian Nuclear Laboratory).The integrated multi-physics model includes:(i) a human pharmacokinetic modelling tool based on the CNL advanced thermalhydraulics code ARIANT (AlgoRIthm for Analysis of Network Thermalhydraulics), with one-dimensional analysis capabilities to track the drug delivery in the vascular system; (ii) a micro- and small-scale dosimetry modelling tool based on Geant4 modelling to predict the dose distribution; (iii) a tool to evaluate the therapeutic responses of tumor cells or nuclear damage to normal cells using GEANT4-DNA.The complete simulation for the distributed absorbed dose in the vascular system and organs generated by administrated Alpha-immuno-conjugate containing Ac-225 will be validated using in vivo pre-clinical studies. The novelty of the toolset compared with the published work makes a more accurate and personalized absorbed dose estimates possible for clinicians.