Establishment of a small animal tumour model for in vivo studies with low energy laser accelerated particles

Background: The long-term aim of developing a laser based acceleration of protons and ions towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short pulsed particle beams. Recent in-vitro data showed similar effects of laser-accelerated versus “conventional” protons on clonogenic cell survival. As the proton energies currently achieved by laser driven acceleration are too low to penetrate standard tumour models on mice legs, the aim of the present work was to establish a tumour model allowing for the penetration of low energy protons (~ 20 MeV) to further verify their effects in vivo.
Methods: KHT mouse sarcoma cells were injected subcutaneously in the right ear of NMRI (nu/nu) mice and the growing tumours were characterized with respect to growth parameters, histology and radiation response. In parallel, the laser system JETI was prepared for animal experimentation, i.e. a new irradiation setup was implemented and the laser parameters were carefully adjusted. Finally, a proof-of-principle experiment with laser accelerated electrons was performed to validate the tumour model under realistic conditions, i.e. altered environment and horizontal beam delivery.
Results: KHT sarcoma on mice ears expressed a high take rate and showed continuous tumour growth after reaching a volume of ~ 5 mm³. The first irradiation experiment using laser accelerated electrons versus 200 kV X-rays was successfully performed and tumour growth delay was evaluated. Comparable tumour growth delay was found between X-ray and laser accelerated electron irradiation. Moreover, experimental influences, like anaesthesia and positioning at JETI, were found to be negligible.
Conclusion: A small animal tumour model suitable for the irradiation with low energy protons was established and validated at a laser based particle accelerator. For this reason, the translation from in vitro to in vivo experimentation was for the first time realized and an important milestone towards the clinical application of laser driven particle accelerators was achieved.