Improving preclinical proton radiation dosimetry using a biologically relevant murine dosimetry phantom

Proton beam therapy is an alternate form of radiotherapy, delivering high energy particles to a tumour. The favourable dose deposition of protons follows a low entrance dose ending in a steep dose gradient and rapid fall off (Bragg peak), increasing the precision of the dose delivery. The size difference between a human and a mouse make it difficult to utilise the Bragg peak distribution within the small animal so often the initial plateau region of the beam is used to irradiate the target. Consequently, healthy tissue beyond the target is irradiated, increasing toxicity. The beam energy can be reduced to deposit the Bragg peak within the animal but this is a complicated process so often range shifters, energy degraders, shielding or collimators are used to attenuate and shape the beam before it reaches the animal. The aim of this study is to adapt a 3D printed murine dosimetry phantom to ensure accurate proton dose delivery in our proton research laboratory. Once validated, this model will be sent to international institutions to perform an audit of the different techniques implemented and the accuracy of delivered dose. This will be facilitated through our existing collaborations with the Inspire project and the Particle Therapy Co-operative Group. Furthermore, 3D cellular models in a hydrogel matrix will be combined with markers of DNA damage to validate the dose distribution. Since 2016, ~1300 mice have been used worldwide in proton research. The phantom could be used to refine research by streamlining experiments to reduce the time the animals are under anaesthesia or immobilised. Increasing confidence in delivered doses will minimise the risk of unnecessary radiation toxicity and reduce the numbers required for statistically significant data. ~200 of these animals were used in pilot studies to validate irradiation techniques and equipment. This 3D printed phantom contains tissue mimicking materials, therefore is a suitable replacement for these animals.