In vivo dose response studies for laser driven particle beams

Purpose. The novel technology of proton and ion acceleration by ultra high intensity lasers promises the realization of compact and economic particle accelerators for cancer therapy that can be integrated in already existing clinics. Before potential clinical application possible biological consequences of laser accelerated and therewith ultra-short pulsed particle beams with high pulse dose have to be investigated. As first step in the chain of translational research extensive in vitro dose response studies with laser driven electron and proton beams were performed within the joint research project “onCOOPtics”. We now report on first experiments comparing laser and conventional accelerated particle beams in vivo.
Material and methods. A mouse tumor model suitable for the currently available still low energy (up to ~30 MeV) of laser accelerated protons was established and successfully implemented using laser accelerated electrons, likewise providing information about biological consequences of ultra-short pulsed beams. To apply a prescribed dose to each tumor the prior established laser based 2D in vitro irradiation technology was enhanced for the 3D animal model in terms of beam transport, beam monitoring, dose delivery and dosimetry. A system for mouse fixation, precise tumor positioning and verification at the irradiation site was realized (Schürer et al. 2012). In vivo tumor irradiation was performed at the 30 TW Jena Titanium: Sapphire (JeTi) laser system. Electron pulses of energies up to a few 10 MeV were generated focusing laser pulses of 28 fs duration into a hydrogen gas jet. Murine sarcoma KHT and human squamous cell carcinoma FaDu tumors were irradiated with doses up to 14 Gy at mean dose rates of 1–2 Gy/min. Reference electron irradiation was performed with the same setup and dosimetry system at a conventional therapy LINAC. The radiation induced tumor growth delay was investigated for several hundred mice.
Results. The irradiation campaign was conducted over a period of several months proving the reliability and stability of all implemented setup components and methods. Dose response curves of both beam qualities have been obtained for the direct comparison of ultra-short pulsed laser accelerated and conventional continuous electron beams. The current status of the ongoing data evaluation gives no evidence for a different RBE of laser driven electrons.
Conclusion. The successful establishment of all technical requirements for and the world wide first performance of systematic animal studies with laser accelerated electrons mark an important step towards the clinical application of laser accelerated particle beams. The realization of in vivo studies with laser driven proton beams is now feasible.
1. M Schürer et al (2012) Irradiation system for pre-clinical studies with laser accelerated electrons. Biomed Tech 57(Suppl. 1):62–65
Supported by BMBF grant nr. 03ZIK455 and 03Z1N511.