An analytical framework for efficient and precision-controlled Monte Carlo simulation of heterogeneous targeted alpha...

Area of Science:

• Medical Physics
• Radiation Oncology
• Nuclear Medicine

Background:

• Microscopic heterogeneity significantly impacts targeted alpha therapy (TAT) dose-effect relationships, highlighting the importance of microdosimetry.
• Monte Carlo (MC) simulation, while accurate, faces computational challenges in TAT microdosimetry due to complexity and inefficiency.
• A systematic and implementable methodology is needed for microdosimetric simulation and analysis in TAT.

Purpose of the Study:

• To establish a quantitative MC simulation framework for TAT microdosimetry.
• To analytically process heterogeneous conditions within the framework.
• To estimate Type A standard uncertainty for derived microdosimetric quantities.

Main Methods:

• Defined elementary-source events and identified raw moments of single-event microdosimetric quantities via MC simulation.
• Modeled heterogeneous environments as weighted mixtures of elementary events and derived analytical error propagation for quantifying standard error.
• Developed a long-range radiation correction for alpha-emitting nuclides to link microscopic energy deposition with macroscopic absorbed dose.

Main Results:

• Implemented a Geant4-based application for heterogeneous microscopic models, validating consistency with direct simulations.
• Utilized MC standard error of single-event dose-mean specific energy as a convergence criterion, compensating for long-range radiation effects.
• Demonstrated efficient factor analysis for diverse heterogeneous conditions and obtained dose-response characteristics consistent with prior TAT studies.

Conclusions:

• The developed framework enables trace-back variance analysis and microdosimetry-compatible variance reduction for precision-controlled MC microdosimetry in TAT.
• Supports flexible analysis of heterogeneity factors, crucial for optimizing targeted alpha therapy.
• Facilitates reliable microdosimetric assessment, advancing the application of TAT.