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  • 1
    Keywords: GROWTH ; IRRADIATION ; radiotherapy ; carcinoma ; THERAPY ; DEPENDENCE ; ACCELERATED ELECTRONS ; FADU
    Abstract: The long-term goal to integrate laser-based particle accelerators into radiotherapy clinics not only requires technological development of high-intensity lasers and new techniques for beam detection and dose delivery, but also characterization of the biological consequences of this new particle beam quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe successful in vivo experiments with laser-driven electron pulses by utilization of a small tumour model on the mouse ear for the human squamous cell carcinoma model FaDu. The already established in vitro irradiation technology at the laser system JETI was further enhanced for 3D tumour irradiation in vivo in terms of beam transport, beam monitoring, dose delivery and dosimetry in order to precisely apply a prescribed dose to each tumour in full-scale radiobiological experiments. Tumour growth delay was determined after irradiation with doses of 3 and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with continuous electron beams at a clinical linear accelerator in order to both validate the dedicated dosimetry employed for laser-accelerated JETI electrons and above all review the biological results. No significant difference in radiation-induced tumour growth delay was revealed for the two investigated electron beams. These data provide evidence that the ultra-high dose rate generated by laser acceleration does not impact the biological effectiveness of the particles.
    Type of Publication: Journal article published
    PubMed ID: 25600561
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  • 2
    Keywords: CELLS ; SURVIVAL ; ELECTRON-BEAMS ; FRACTIONATED-IRRADIATION
    Abstract: 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 mouse legs, the aim of the present work was to establish a tumour model allowing for the penetration of low energy protons (ca. 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 showed a high take rate and continuous tumour growth after reaching a volume of ca. 5 mm(3). 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 particles was established and validated at a laser based particle accelerator. Thus, the translation from in vitro to in vivo experimentation was for the first time realized allowing a broader preclinical validation of radiobiological characteristics and efficacy of laser driven particle accelerators in the future.
    Type of Publication: Journal article published
    PubMed ID: 24533586
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  • 3
    Keywords: IRRADIATION ; carcinoma ; radiation ; CANCER-CELLS ; MAMMALIAN-CELLS ; RELATIVE BIOLOGICAL EFFECTIVENESS ; X-RAY ; GAMMA-H2AX FOCI ; LASER-ACCELERATED ELECTRONS ; ENERGY-DEPENDENCE
    Abstract: PURPOSE: In line with the long-term aim of establishing the laser-based particle acceleration for future medical application, the radiobiological consequences of the typical ultra-short pulses and ultra-high pulse dose rate can be investigated with electron delivery. MATERIALS AND METHODS: The radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance) was used to mimic the quasi-continuous electron beam of a clinical linear accelerator (LINAC) for comparison with electron pulses at the ultra-high pulse dose rate of 10(10) Gy min(-1) either at the low frequency of a laser accelerator or at 13 MHz avoiding effects of prolonged dose delivery. The impact of pulse structure was analyzed by clonogenic survival assay and by the number of residual DNA double-strand breaks remaining 24 h after irradiation of two human squamous cell carcinoma lines of differing radiosensitivity. RESULTS: The radiation response of both cell lines was found to be independent from electron pulse structure for the two endpoints under investigation. CONCLUSIONS: The results reveal, that ultra-high pulse dose rates of 10(10) Gy min(-1) and the low repetition rate of laser accelerated electrons have no statistically significant influence (within the 95% confidence intervals) on the radiobiological effectiveness of megavoltage electrons.
    Type of Publication: Journal article published
    PubMed ID: 25968557
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