Laser particle accelerators for radiotherapy: first in vitro cell experiments with laser accelerated electron beams

Objective
The novel technology of particle acceleration based on high intensity laser systems promises accelerators of compact size and reasonable costs and may significantly contribute to a widespread use of high precision hadron radiotherapy. Although some basic properties of laser acceleration are reasonably well known from theory, simulations and fundamental physical experiments, several further requests have to be fulfilled for its medical application such as supply of a stable and reliable particle beam with reproducible properties and precise delivery of dose in an appropriate irradiation time with required exposure of a desired irradiation field. Moreover, the ultra-short pulsed (in the region of 100 fs) particle beams with resulting high pulse dose-rate (more than 1012 Gy/min) have to be characterized with regard to there radiobiological properties. 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.

Material and Methods
Experiments have been performed at the Jena Titanium:Sapphire 10 terawatt laser system JeTi. Laser pulses (80 fs duration, 2.5 Hz repetition rate) were focused into a helium gas jet, accelerating electrons to energies of up to few ten MeV. Before irradiation, the JeTi system was optimized for cell experiments: the electron spectrum was limited to a minimum energy of 3 MeV, the beam spot size was adjusted and the dose rate and homogeneity were improved. Cell irradiations with doses in the range of 0.3 to 10 Gy have been performed for two squamous cell carcinoma (FaDu, SKX) and two normal tissue (mammary gland epithelial cells 184A1, human skin fibroblasts HSF2) cell lines. Each sample was equipped with two Gafchromic EBT radiochromic films, one in front and one behind the cell monolayer, used for retrospective precise dose determination. A Roos ionization chamber and a Faraday Cup monitored the beam providing on-line dose information necessary for irradiation control.
Following to the irradiation the cell survival fraction was determined using clonogenic survival assay. In addition, DNA double strand breaks present in cell 24 h after irradiation were analyzed by immunochemical detection of co-localized gamma-H2AX and 53BP1 molecules. Reference irradiation with a conventional X-ray tube (200 kV) was performed in parallel with experiments at JeTi.

Results
Normally used for physical single-shot experiments, the JeTi was customized for a long-time cell irradiation. Samples were irradiated at 13 experiment days over a period of 10 weeks. A reasonably stable and reproducible beam was achieved. Reviewed as average out of all cell irradiations a mean dose per pulse of 2.4 mGy was obtained. Comparing all samples, a variation in beam intensity of up to 40 % within one day and up to 130 % within all days was observed, but was compensated during cell irradiations by means of the on-line dose monitoring system. Dose homogeneity was examined for all samples within the target area and the inhomogeneity obtained was less than 10 % for all days and all applied doses. Although still preliminary, the dose-effect-curves obtained show in general a lower biological effectiveness for the laser accelerated electron beams in comparison with conventional X-rays. Possible reasons will be discussed.

Conclusions
Further experiments are prepared at a 100 terawatt laser system, which will lead to enhanced energy and intensity of the electron beam but also provide laser accelerated proton beams for cell irradiation studies.

The work was supported by the BMBF, grant no. 03ZIK445