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Targeted alpha therapies using 211At: A Geant4 simulation of dose and DNA damage
Chiara De Sio1, Laura Ballisat1, Lana Beck1
1School of Physics, University of Bristol, Bristol, UK.
Summary
Targeted alpha therapies using Astatine-211 (At-211) show promise for localized cancer treatment. Simulations reveal alpha particles induce DNA damage within 80μm, supporting their use against micrometastases.
Area of Science:
- Medical physics
- Radiation oncology
- Nuclear medicine
Background:
- Targeted alpha therapies (TAT) offer high efficacy for cancer treatment due to high linear energy transfer (LET) and short particle range.
- Astatine-211 (At-211) is a radionuclide utilized in ongoing clinical trials for TAT.
- Understanding initial radiation damage is key for optimizing TAT treatment planning.
Purpose of the Study:
- To simulate absorbed dose profiles and DNA damaging potential of intravenously administered TAT using At-211.
- To assess the localized biological effect of At-211 alpha particle emission from blood vessel walls.
Main Methods:
- Geant4(-DNA) based simulations were employed.
- Calculations focused on absorbed dose and DNA damage in tissues surrounding a blood vessel wall.
- Radionuclide decay was simulated on the blood vessel wall.
Main Results:
- The therapeutic effect is primarily attributed to alpha particles, with localized effects up to 80μm from the vessel.
- Relative biological effectiveness (RBE) ranged from 2.5 to 4, calculated based on DNA double-strand breaks.
- Simulations quantified the absorbed dose and DNA damage potential.
Conclusions:
- At-211 TAT is effective within the short range of its alpha particles.
- The ability to induce complex DNA damage over a short distance makes At-211 promising for localized treatment of small tumors or micrometastases.
