Evaluating very high energy electron RBE from nanodosimetric pBR322 plasmid DNA damage

Area of Science:

• Medical physics
• Radiation biology
• Particle physics

Background:

• Very High Energy Electrons (VHEE) are a novel modality for radiotherapy.
• Understanding the biological effectiveness of VHEE is crucial for clinical translation.
• Previous studies have not investigated VHEE's biological effects at energies relevant to particle therapy.

Purpose of the Study:

• To determine the Relative Biological Effectiveness (RBE) of VHEE using plasmid DNA irradiation.
• To investigate the mechanisms of DNA damage (direct vs. indirect effects) induced by VHEE.
• To assess the potential for a FLASH effect with VHEE at high dose rates.

Main Methods:

• Plasmid DNA irradiation with VHEE (100-200 MeV) at CERN's CLEAR facility.
• Measurement of DNA damage yields (specifically Double-Strand Breaks - DSBs) in dry and aqueous conditions.
• Utilizing GEANT4-DNA for track structure simulations based on experimental damage yields.
• Comparison of DSB yields at conventional and high (FLASH) dose rates.

Main Results:

• Approximately 99% of DNA breaks were caused by indirect effects, consistent with protons and photons.
• Calculated RBE values for VHEE were comparable to established radiotherapy modalities.
• GEANT4-DNA simulations showed reasonable agreement with experimental DSB yield data.
• No significant variation in DSB yield was observed between conventional and FLASH dose rates for VHEE.

Conclusions:

• VHEE exhibits physical and biological damage characteristics similar to conventional radiotherapy, supporting its clinical potential.
• Indirect effects are the primary mechanism of DNA damage induced by VHEE.
• Under the tested conditions, VHEE does not demonstrate a FLASH radiotherapy effect.