Radiobiology Research at MedAustron – Ion Therapy and Research Centre Sylvia Gruber, PhD Medical University of Vienna High Energy Physics Seminars Imperial College London
Contents
The MedAustron Centre • • •
A Brief History
Tumour Therapy Options
Ion Beam Therapy: Physical Motivation Superior dose distribution • • •
Ion Beam Therapy: Biological Motivation Increased Effectiveness • • •
Ion Beam Therapy: Indications • • •
Facility Layout
Pencil Beam Scanning
Irradiation Rooms
Irradiation Rooms – Patient Treatment
Current Treamtents at MedAustron Head & Neck Skull Base Sarcoma CNS Pediatric Tumours Prostate Re-Irradiation • •
Irradiation Rooms - Research
Irradiation Room 1 • • • • • • •
Non Clinical Research Groups
Applied and Translational Radiobiology Team
Timeline of ATRAB at MedAustron 53BP1
Mission Broadening of the therapeutic index • •
Focus of Radiobiological Research at MedAustron Challenging the RBE • • • • •
RBE Dependencies: Tissue Characteristics
RBE Dependencies: LET •
RBE Dependencies: LET
RBE Dependencies: Target Coverage Energy • • • •
RBE Dependencies: Target Coverage Energy and LET • • • • • • 66.5 – 135.6 MeV • 137.2 – 180.1 MeV
Dosimetry Aspects
Dosimetry Aspects
Squamous Cell Carcinoma Cells
Normal Skin Keratinocytes
Prostate Carcinoma Cells
A 3D World
Advances Cell Culture Models: Multicellular Tumor Spheroids
Advances Cell Culture Models: Multicellular Tumor Spheroids
Therapy-relevant Factor: Hypoxia Indirect vs. direct DNA damage • • • • •
Spheroid Size determines Oxygen Gradient • •
DNA Damage: Influence of 3D Tissue Architecture Squamous Cell Carcinoma Spheroids
Tumor Spheroids: Irradiation Setup •
Tumor Spheroids: Irradiation Setup
Résumé and Workaround • • • • •
Advances Cell Culture Models: Biomimetic Epithelium
Radiobiology of Normal Tissue Reactions functional layer germinal layer submucosa tongue muscle (n th gen)
The Oral Mucositis Mouse Model
Normal Tissue Protection: Dermatan Sulfate for OM Mitigation
DS-mediated radioprotection: not stimulation of proliferation but junctions Fraction of BrdU positive cells (%) / 140 200 14 Epithelial cell numbers (%) *** Epithelial thickness (µm) germinal epithelial layer 12 120 150 10 100 *** * 8 ** ** 100 6 80 4 50 60 2 40 0 0 0 2 4 6 8 10 12 14 0 2 4 6 8 10 12 14 0 2 4 6 8 10 12 14 days after onset of irradiation days after onset of irradiation days after onset of irradiation
DS-mediated radioprotection: reduced hypoxia
DS-mediated radioprotection: reduced inflammation
MedAustron - Outlook • • •
Research Outlook – 2019-2021 Correlation of LET and signalling events • • • • •
Acknowledgement http://www.meduniwien.ac.at/hp/radonc/ • • • • • • The financial support by the Federal Ministry for Digital and Economic Affairs and the National Foundation for Research, Technology and Development is gratefully acknowledged.
Supplementary
Accelerator Components – Ion Sources • • • • • • • •
Accelerator components – Low Energy Beam Transfer Line • • • • • •
Accelerator components – Linear Accelerator • • • • •
Accelerator components – Synchotron • • • • • • • •
Accelerator components – High Energy Transfer Line • • • • • •
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