BACKGROUND

Radiobiological data suggests variations in relative biological effectiveness (RBE) between clinically used photon-based sources. A microdosimetric formalism using Monte Carlo (MC) methods can mechanistically describe the photon RBE. Experimentally derived RBE based on DNA double-strand breaks ( ) has been shown to scale with the microdosimetry quantity dose-mean lineal energy ( ).

PURPOSE

To calculate microdosimetric spectra for clinically relevant photon sources, spanning from soft x-rays produced by a 50 kVp x-ray source through various brachytherapy sources up to a 6 MV medical linac. Furthermore, we investigated the correlation between and of different photon sources.

METHODS

Photon sources simulated include low-energy x-rays (50 kVp), orthovoltage x-rays (225 kVp), high-dose-rate brachytherapy sources (Se, Ir and Co), and a 6 MV medical linac. Secondary electron spectra at the cellular level were calculated for in vitro cell irradiation setups using Geant4 MC-based packages, RapidBrachyMCTPS and RapidExternalBeam. The obtained spectra were used in MicroDose, a microdosimetry simulation software, to obtain microdosimetric quantities, including single-event lineal energy ( ) and specific energy ( ) spectra, and dose-mean and frequency-mean quantities ( , , , ). Uniform spherical targets (1-14  radius) and realistic HeLa and PC3 cell nucleus models were simulated using cell size data obtained from literature and nuclei size data from confocal microscopy imaging. Radiobiological experiments using foci quantified DNA double-strand breaks for HeLa and PC3 cells after irradiations with 50 and 225 kVp, Ir, and 6 MV linac, and was determined using 225 kVp as the reference.

RESULTS

The calculated ( ) is within the 3.5-1.2 keV/ range (1.8-0.2 keV/ ) for 1  simulated target size between the lowest energy 50 kVp x-ray source and the highest energy 6 MV linac source, respectively. For the HeLa and PC3 cell nuclei models based on microscopy data, ( ) spans from 1.6 to 0.6 keV/ (0.7 to 0.2 keV/ ). When compared between different target sizes, ( ) ranges from 3.5 to 1.0 (1.8-0.4) keV/ between 1 and 10  radius targets for the 50 kVp x-ray source. A smaller change is observed for 6 MV linac, ranging from 1.2 to 0.5 keV/ and 0.23 to 0.22 keV/ for and , respectively. For the simulated Se source currently under investigation, the calculated values are 11%-24% higher relative to those of Ir in the range of target sizes between 1 and 14  in radius. for HeLa cells was 1.4 0.7 for 50 kVp x-rays, 0.5 0.2 for Ir, and 0.7 0.4 for 6 MV linac irradiations. For PC3 cells, was 1.3 0.6, 0.8 0.4 and 0.5 0.3 for 50 kVp, Ir and 6 MV linac, respectively. Measured values are consistent with ratios of the corresponding photon sources for HeLa and PC3 nucleus models.

CONCLUSIONS

Microdosimetric spectra strongly depend on the simulated energy of photon sources and target size, with and decreasing by a factor of 2-3 between diagnostic 50 kVp and 6 MV therapeutic x-rays for target sizes from 1-14 in radius. The early damage indicates this stochastic change in energy density between various photon sources as the yields of foci per nucleus scale with of the source.