Modelling single cell dosimetry and DNA damage of targeted alpha therapy using Monte-Carlo techniques

Area of Science:

• Nuclear medicine
• Radiation oncology
• Medical physics

Background:

• Targeted alpha therapy (TαT) uses alpha-emitting radioisotopes for precise tumor cell irradiation.
• Four radionuclides (Actinium-225, Radium-223, Lead-212, Astatine-211) are promising for TαT.

Purpose of the Study:

• To simulate absorbed dose and DNA damage from four TαT radionuclides.
• To evaluate the impact of radionuclide distribution within a cell model on radiation dose and efficacy.

Main Methods:

• Monte Carlo simulations using TOPAS and TOPAS-nBio (Geant4, Geant4-DNA).
• Modeling alpha particle transport and decay in a spherical cell model.
• Simulating radionuclide distribution on the cell membrane, cytoplasm, nucleus surface, and within the nucleus.

Main Results:

• Higher absorbed doses to the nucleus per decay were observed when radionuclides were located on the nucleus wall or within the nucleus.
• Actinium-225 and Radium-223 showed higher doses per decay than Lead-212 and Astatine-211 due to longer decay chains and higher alpha yields.
• Astatine-211 demonstrated high relative efficacy when distributed within or on the nucleus surface, indicated by absorbed dose and DNA strand breaks.

Conclusions:

• Radionuclide localization within the cell nucleus is critical for maximizing absorbed dose and therapeutic efficacy in TαT.
• Targeting tumour cell nuclei with specific molecules is recommended to optimize TαT outcomes.
• Further research into nucleus-targeted radionuclide delivery can enhance cancer treatment strategies.