Biological dosimetry following synchrotron microbeam radiation therapy

Full text: Synchrotron microbeam radiation therapy (MRT) is based on observations that normal tissue displays a remarkable resistance to necrosis when irradiated with parallel, thin slices of X-rays. Additional findings suggest that tumour tissue is destroyed by MRT at doses that leave surrounding normal tissues relatively undamaged. The biological effects of MRT are not well understood, and are complicated by difficulties in measuring the MRT radiation doses delivered to the tissue. The aim of this study was to analyse MRT-induced DNA damage responses in a selection of normal and malignant cell lines, and murine skin, and to biologically assess the dose delivered to the 'valley' regions between microbeam peaks. Immunohistochemical staining for phosphorylation of histone H2AX (gamma-H2AX), a marker for DNA double-strand breaks, revealed intense 'stripes' of positive staining at locations where microbeams had traversed the tissue. The widths of these stripes were similar to the nominal physical beam width of 25 micrometres. Scoring of gamma-H2AX foci in regions between MRT tracks was utilised as a biodosimetric assay to biologically determine the dose delivered to valley dose-irradiated tissues. Foci yields in spared tissue were compared with foci yields induced by broadbeam exposure to known low doses from synchrotron X-rays and a g-ray source. We observed that about 3% of the peak MRT dose was delivered to central 'valley' regions. In conclusion, gamma-H2AX is a sensitive and quantitative biomarker for radiation exposure which may be employed to visualise, quantify and validate dose distributions delivered to tissues in microbeam radiotherapy regimens. (author)