ESTRO 2022 - Abstract Book

S71

Abstract book

ESTRO 2022

Figure 1. SR-FTIRM results. Principal Component Analysis (PCA) (Left: PC1-PC2; Centre: PC2-PC3; Right: Loading plot) showing the differences between the several groups (Control: Ctrl; Broad beam: BB; Peak region in MBRT: MB_P; Valley region in MBRT: MB_V). Each point represents a cell spectrum. Conclusion Our study highlighted the relevance of SR-FTIRM as a useful and precise technique for assessing the biochemical cell response to innovative radiotherapy approaches. Results provided new insights into the molecular changes in response to MBRT treatments using neon beams. However, monitoring of overall cell response upon Ne MBRT is a complex task since it involves a wide range of biochemical processes. The full understanding of the underlying biology in such novel approaches will require further investigations. T. Suckert 1,2 , E. Beyreuther 1,3 , N. Bürger 4,5 , J. Müller 6 , E. Bodenstein 1 , M. Meinhardt 4 , M. Boucsein 7,9 , E. Bahn 7,8,9,10 , P. Hönscheid 2,4,5 , M. Krause 1,2,5,11,12 , A. Dietrich 1,2 1 OncoRay, National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technical University (TU) Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; 2 German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, Germany; 3 Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiation Physics, Dresden, Germany; 4 University Hospital Carl Gustav Carus, Institute of Pathology, Dresden, Germany; 5 National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany; 6 Technical University Dresden, DFG Cluster of Excellence “Physics of Life”, Dresden, Germany; 7 German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg, Germany; 8 Heidelberg Institute of Radiation Oncology (HIRO), Quantitative klinische Strahlenbiologie, Heidelberg, Germany; 9 Heidelberg University Hospital, Radiation Oncology, Heidelberg, Germany; 10 National Center for Tumor Diseases , Integrative Radiation Oncology, Heidelberg, Germany; 11 Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiooncology, Dresden, Germany; 12 University Hospital Carl Gustav Carus, Department of Radiotherapy and Radiation Oncology, Dresden, Germany Purpose or Objective Proton therapy enables the protection of tumor-surrounding normal tissue; nevertheless, some patients develop late radiation-induced brain injury following brain tumor treatment. In clinical follow-up, it is often difficult to differentiate between radiation-induced brain injury, pseudoprogression, or tumor recurrence. Therefore, biomarkers are needed to identify the right therapy option for the individual patient. In addition, the biological mechanisms underlying radiation- induced normal tissue damage are still not fully understood and further investigations are necessary to discover new treatment options. A promising method for in situ molecular research is MALDI imaging, an innovate type of mass spectrometry that provides lipidomics and proteomics data with high spatial resolution. We now applied this method to our mouse model for radiation-induced brain injury [1,2] following proton therapy to shed light on normal tissue side effects. Materials and Methods A cohort of 30 C57BL/6 mice received either sham treatment or proton irradiation of a brain subvolume with 50 Gy single fraction at the experimental beam line of the University Proton Therapy Dresden as described in [1,2]. During follow-up, the animal health was scored bi-weekly. A subset of mice was sampled at two, four and six months post irradiation after acquiring a final MRI. MALDI imaging was performed on one representative section containing the dose maximum of the beam. This tissue section was subsequently stained for H&E and evaluated by a neuropathologist. Results All animals developed a skin reaction grade 1 within the irradiation field, but no other health deterioration was observed. Evaluation of contrast-enhanced volume in T1-weighed MRI showed progressing brain injury, with a large inter-individual variation at the latest time point. Some animals from the 6-month cohort had additional hypointensities in the T2-weighted MR images within the region of the dose maximum. Only minor tissue changes were detected in the H&E staining. On the other hand, MALDI imaging revealed specific mass-to-charge (m/z) values that decrease within the irradiated brain area and remain for up to 6 months, indicating declining protein and lipid levels related to radiation-induced brain injury. All imaging modalities, including a Monte-Carlo dose simulation and a mouse brain atlas were registered to the m/z distribution maps for multi-dimensional correlations. OC-0096 MALDI imaging detects lipid and peptide changes in a mouse model of radiation-induced brain injury