Introduction
Ion beam therapy, utilizing protons and Carbon ion beams, represents the forefront of cancer treatment involving ionizing radiation. When compared to photon therapy, ion beams exhibited superior physical and biological characteristics. However, there is a fundamental lack of radiobiological research in particle therapy at the molecular, cellular, and tissue levels based on high-quality physics data. To foster future advancements in ion beam therapy, interdisciplinary pre-clinical research based on tumour models assumes essential importance. Nevertheless, new technologies in the context of particle beam therapy for small animal research bring an extensive range of challenges that need careful assessment, ranging from imaging for treatment planning including dose and linear energy transfer (LET) determination, precision dose delivery, animal imaging for tissue characterization and response assessment and correlation of advanced imaging with histopathology.
Objectives and Faculty
Thus, the overarching objective of the FWF-funded PAIR (PreclinicAl Ion beam Research) project is to bridge the knowledge gap in radiobiology pertaining to ion beams, encompassing the molecular, cellular, and tissue levels by introducing novel approaches in pre-clinical research.
To accomplish this, the PAIR project involves collaboration between senior scientists and their research groups at the MedUni Vienna, the Vetmeduni Vienna, the FHWN as well as the cooperation partner MedAustron. This interdisciplinary scientific network comprises five PhD projects that combine the fields of physics, cancer biology, and bioinformatics to provide a systematic understanding of how ion therapy impacts cellular outcomes, including signal transduction and genome stability.
Methods
The research focuses on establishing a link between in-vitro and in-vivo molecular radiobiological approaches, functional/metabolic multiparametric imaging, and conducting radiomics analyses. Macroscopic (e.g. absorbed dose) and microscopic physics parameters (e.g. LET) are merged with a systematic understanding of how ion therapy can impact cellular outcomes, with a particular emphasis on genomics and proteomics analyses of models. This would be coupled with advanced ultra-high-field (UHF) magnetic resonance imaging for better tumour characterization, both at the mechanistic and methodological levels. Such integration allows for a comprehensive understanding of the relationship between cellular responses and the imaging biomarkers associated with dose and linear energy transfer. Moreover, 3D tumour models/spheroids to conduct molecular analyses are used, focusing on genome stability, mutagenesis, transcriptional regulation, and cell death. Furthermore, in-vitro molecular radiobiological methods are complemented with in-vivo models (animal model) for a more clinically relevant tumour environment investigation.
Added value
The PAIR project aims to strengthen the innovation capacity in Austria by creating a new research and educational network in the Greater Vienna area within the field of clinical particle therapy. The highly complementary scientific and educational expertise of the faculty members, combined with the unique infrastructure for pre-clinical particle therapy research in Austria, will contribute to the advancement of current knowledge and methods in ion beam research, which in turn will have a major impact on clinical particle therapy.