Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf
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Normal tissue reaction following proton irradiation of the mouse brain
Background: Due to the beneficial inverse physical depth-dose profile, proton radiotherapy (PT) offers the potential to reduce normal tissue toxicity by depositing the maximum dose within the tumor volume while sparing the surrounding tissue. However, range uncertainties and necessary clinical safety margins in combination with varying relative biological effectiveness may result in a critical dose in the normal tissue. Dedicated preclinical studies are needed to assess and better understand potential adverse effects of PT and to develop potential biomarkers and countermeasures for backtranslation into clinics.
For this purpose, a high-precision image-guided proton irradiation setup for small animals was established at the University Proton Therapy Dresden that mimics the clinical workflow, including pre-treatment imaging, treatment planning and image-guided brain irradiation.
The right hippocampus of C57BL/6 and C3H/HeN mice was irradiated to study the dose- and time-dependent radiation response of mouse brain tissue after short or long-term follow-up analysis. A Monte Carlo model of the proton beam was designed in the simulation toolkit TOPAS to calculate the dose distributions in vivo and to correlate the outcome with proton dose and LET.
The geometric accuracy of proton irradiation, detailed dose simulations on mouse CT and cell-based assessment enable a biologically and spatially resolved analysis of short-term radiation response and RBE. In addition, the long-term follow up over six month provides first insights into the formation of normal tissue damage in mouse brain after PT.
digital-ERRs, 13.-17.09.2020, Lund, Sweden