Laser particle accelerators for radiotherapy – first radiobiological in vitro cell characterisation

The novel technology of particle acceleration based on high intensity laser systems promises radiotherapy accelerators of compact size and reasonable costs. Laser acceleration results in ultra-short pulsed particle beams (in the region of 100 fs) with very high pulse dose rate (more than 1012 Gy/min) and is used in single shot physics experiments so far. Before a conceivable clinical application such particle beams have to be characterized in terms of their radiobiological properties and dosimetric detection and must allow a stable and reliable dose delivery. First in vitro cell irradiations with laser accelerated electron beams were performed and dose-effect-curves were obtained for four cell lines and two endpoints. Experiments have been performed at the Jena Titanium:Sapphire 10 terawatt laser system JETI, accelerating electrons to energies of up to 20 MeV. Before cell irradiation, the JETI system was optimized, adjusting the electron energy and beam spot size and improving the dose rate and homogeneity. Cell irradiations with doses in the range of 0.3 to 10 Gy have been performed for two squamous cell carcinoma cell lines with different radiosensitivity (FaDu, SKX) and two normal tissue cell lines (mammary gland epithelial cells 184A1, human skin fibroblasts HSF2). Each sample was equipped with radiochromic films used for retrospective precise dose determination. A Roos ionization chamber and a Faraday Cup monitored the beam providing online dose information necessary for irradiation control. Following to the irradiation the cell survival fraction was determined using clonogenic survival assay. Furthermore DNA double strand breaks were analyzed by immunochemical detection of the colocalized γH2AX and 53BP1 proteins 24 h after irradiation. Reference irradiation with a conventional X-ray tube (200 kV) was performed in parallel with experiments at JETI.
Samples were irradiated over a period of 3 months with described doses in which a reasonably stable and reproducible beam could be achieved monitored by the reliable accurate dosimetry system. The dose-effect-curves obtained indicate a lower biological effectiveness for the ultra-short pulsed laser accelerated electron beams in comparison with continuous X-rays. Possible reasons could be the different energy spectra impacting on cells as well as the low mean and ultra-high pulse dose rate of the electron beam. The effects will be discussed based on further experimental results.
This work has been supported by the German Federal Ministry of Education and Research (BMBF), grant no. 03ZIK445.