Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Objective: From the various factors that are known to influence the radiobiological response to therapeutic beams, the radiation type and beam energy or LET (linear energy transfer), and the beam pulsing and dose rate are object of comprehensive investigations. Alterations of these parameters might result in altered damage pattern and consequently in a different radiobiological effectiveness, for example for the FLASH, single pulse, irradiation regime [1] and the use of multiple, ultra-short laser driven particle pulses [2] where therapeutic relevant doses are administered within the fraction of a second, i.e. at high dose rate. To characterize the influence of radiation quality, i.e. beam energy, dose rate and pulsing, systematic in vitro studies performed at different accelerators will be summarized in the talk.
Methods and results: Two normal human cell lines were applied to study the response to photons in the range of 10 kV to 34 MV, to conventional and laser driven electrons, and to continuous and pulsed proton beams. By measurements of chromosomal aberrations and DNA double-strand breaks (DSB) the inverse correlation of photon energy and biological damage was revealed, whereas for the proton studies no clear influence of pulsing was found. Furthermore, no influence on clonogenic survival was observed comparing laser driven electrons of ultra-high dose rate (109 Gy/s, multiple electron pulses) and conventional, linac electrons (continuous dose rate 3 Gy/min). By contrast, a trend towards less effectiveness of pulsed laser driven electrons was revealed by measurements of residual DNA DSB. To investigate this finding in more detail, radiobiological experiments were performed at the superconducting research electron linac ELBE, which is able to provide electron beams with very variable pulse sequences and to mimic both laser driven and clinical linac electron beams. Thereby, the DSB studies were complemented by DSB repair kinetics.
Conclusion:
Comprehensive in vitro studies of the effects of various radiation qualities revealed the influence of beam energy and LET, but show no clear result with respect to pulse structure and dose rate.
References:
[1] Favaudon et al. Sci Transl Med. 2014;6(245):245ra93.
[2] Karsch et al. Acta Oncol. 2017;56(11):1359-1366.