Subcellular Spatial Correlation of Particle Traversal and Biological Response in Clinical Ion Beams

Purpose To report on the spatial correlation of physical track information (fluorescent nuclear track detectors, FNTDs) and cellular DNA damage response by using a novel hybrid detector (Cell-Fit-HD). Methods and Materials The FNTDs were coated with a monolayer of human non-small cell lung carcinoma (A549) cells and irradiated with carbon ions (270.55 MeV u−1 , rising flank of the Bragg peak). Phosphorylated histone variant H2AX accumulating at the irradiation-induced double-strand break site was labeled (RIF). The position and direction of ion tracks in the FNTD were registered with the location of the RIF sequence as an ion track surrogate in the cell layer. Results All RIF sequences could be related to their corresponding ion tracks, with mean deviations of 1.09 μm and −1.72 μm in position and of 2.38° in slope. The mean perpendicular between ion track and RIF sequence was 1.58 μm. The mean spacing of neighboring RIFs exhibited a regular rather than random spacing. Conclusions Cell-Fit-HD allows for unambiguous spatial correlation studies of cell damage with respect to the intracellular ion traversal under therapeutic beam conditions.