Modelling proton bunches focussed to submicrometre scales: low-LET radiation damage in high-LET-like spatial...

Microbeam experiments approximating high-LET tracks by bunches of lower-LET particles focussed to submicrometre scales (Schmid et al. 2012, Phys. Med. Biol. 57, 5889) provide an unprecedented benchmark for models of biological effects of radiation. PARTRAC track structure-based Monte Carlo simulations have verified that focussed 20 MeV proton bunches resemble the radial dose distributions of single 55 MeV carbon ions as used in the experiments. However, the predicted yields of double-strand break and short (<1 kbp) DNA fragments by focussed protons correspond to homogeneous proton irradiation and are much smaller than for carbon tracks. The calculated yields of dicentrics overestimate the effect of focussing but reproduce the fourfold difference between carbon ions and homogeneously distributed protons. The extent to which focussed low-LET particles approximate high-LET radiation is limited by the achievable focussing: submicrometre focussing of proton bunches cannot reproduce local nanometre clustering, i.e. DNA damage complexity characteristic of high-LET radiation.