In situ biological dose mapping estimates the radiation burden delivered to 'spared' tissue between synchrotron X-ray microbeam radiotherapy tracks

  • Rothkamm K
  • Crosbie J
  • Daley F
 et al. 
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Abstract

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays
can destroy tumours in animal models whilst causing little damage to
normal tissues. Determining the spatial distribution of radiation doses
delivered during MRT at a microscopic scale is a major challenge. Film
and semiconductor dosimetry as well as Monte Carlo methods struggle to
provide accurate estimates of dose profiles and peak-to-valley dose
ratios at the position of the targeted and traversed tissues whose
biological responses determine treatment outcome. The purpose of this
study was to utilise gamma-H2AX immunostaining as a biodosimetric tool
that enables in situ biological dose mapping within an irradiated tissue
to provide direct biological evidence for the scale of the radiation
burden to `spared' tissue regions between MRT tracks. Gamma-H2AX
analysis allowed microbeams to be traced and DNA damage foci to be
quantified in valleys between beams following MRT treatment of
fibroblast cultures and murine skin where foci yields per unit dose were
approximately five-fold lower than in fibroblast cultures. Foci levels
in cells located in valleys were compared with calibration curves using
known broadbeam synchrotron X-ray doses to generate spatial dose
profiles and calculate peak-to-valley dose ratios of 30-40 for cell
cultures and approximately 60 for murine skin, consistent with the range
obtained with conventional dosimetry methods. This biological dose
mapping approach could find several applications both in optimising MRT
or other radiotherapeutic treatments and in estimating localised doses
following accidental radiation exposure using skin punch biopsies.

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