Establishment of small animal irradiation at University Proton Therapy Dresden

Introduction: It is a common practice to use a fixed relative biological effectiveness (RBE) of 1.1 when planning treatments and analyzing outcomes for proton therapy. In contrast, a multitude of in vitro experiments demonstrate variable RBE values. Also, some clinical evidence of RBE variability is emerging, especially at the distal edge of proton treatment fields, showing increased risk of normal tissue complications. However, only a limited number of in vivo trials have been performed to confirm such results. This contribution presents an irradiation setup to study adverse effects in mouse brains induced at proton field edges.
Methods: The mouse is fixated (teeth, ears) in a closed sterile 3D printed holder specifically designed for CT and MR imaging as well as for irradiation with X-rays and protons. Target delineation based on CT and MR imaging can be performed before irradiation. Image-guided positioning of the target volume is achieved by proton radiography [1] with the mouse in treatment position.
In a first brain toxicity study, the distal edge of a laterally collimated clinical proton field (150 MeV) will be positioned in the proximal hemisphere of the mouse brain by inserting polycarbonate plates in front of the mouse holder. For different beam settings, dose distributions in treatment position were obtained with radiochromic EBT3 films placed in plastic phantoms within the mouse holder. Variation of the proton beam range and lateral shape with the amount of decelerating material and collimator size, respectively, were analyzed and used to build a proton beam model. The beam intensity, measured with an ionization chamber, was correlated with the EBT3 film dose measurements at treatment position. This allows for a controlled irradiation of the brain volume with predefined and absolute dose values.
Results and Conclusion: All requirements for systematic proton irradiation experiments in vivo are established at the University Proton Therapy Dresden including target volume delineation, mouse positioning, and dosimetry. First experiments comparing brain toxicity after proton irradiation of one hemisphere relative to photon treatment are in progress.
Reference: [1] Müller et al. Acta Oncologica 2017