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Session: Proton Therapy II [Return to Session]

Expanding Microdosimetry to Include Indirect Damage Induced by Protons and Alpha Particles

A Bertolet*, G Tamborino, H Paganetti, J Schuemann, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA


TU-D1030-IePD-F7-2 (Tuesday, 7/12/2022) 10:30 AM - 11:00 AM [Eastern Time (GMT-4)]

Exhibit Hall | Forum 7

Purpose: Radiobiological effects induced by protons and alpha particles vary with the density of ionizations produced around their track. Microdosimetry aims at modeling microscopic patterns of energy deposition, related to the direct damage induced by radiation, but it lacks methods to include indirect damage by radicals produced after water radiolysis. This work uses simulations in the Monte Carlo code TOPAS-nBio to incorporate the indirect effect into the microdosimetry framework.

Methods: Three different simulations were performed for the same set of monoenergetic protons and alpha particles. We obtained: (i) microdosimetric distributions in liquid-water spherical sites of 1 μm-diameter and dose-mean lineal energy yD were obtained; (ii) G-values for hydroxyl (⋅OH) radicals (i.e., radicals per 100 eV deposited) in the same volume from 1 ps to 3 ns after irradiation; and (iii) the number of single breaks (SBs) and double strand breaks (DSBs) induced by radicals in a nucleus with the whole human genome present (about 6 Gbp) simulated with TOPAS-nBio.

Results: The number of scavenged radicals over time increases with yD due to the higher recombination of radicals in denser ionization clusters. The average number of radicals along the considered time -i.e., radicals susceptible to interact with DNA- was found to be approximately proportional to yD for protons and part of the alpha particle energy range. A saturation effect was observed at the highest yD values for alpha particles. Induced indirect damage was shown to be proportional to the number of generated radicals for both protons and alpha particles, with about 18 breaks/Gbp per 100 ⋅OH radicals in 1 μm.

Conclusion: This work shows how microdosimetry relates to the production of hydroxyl radicals and the induced indirect or mixed (direct+indirect) damage, paving the way for an expanded theory of microdosimetry capable to capture chemistry of water radiolysis besides purely physical phenomena.

Funding Support, Disclosures, and Conflict of Interest: This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI) grant no. K99 CA267560 'Radiation dosimetry for alpha-particle radiopharmaceutical therapy and application to pediatric neuroblastoma'


Radiobiology, Microdosimetry, Monte Carlo


TH- Radiobiology(RBio)/Biology(Bio): RBio- Particle therapy- other

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