Abstract
BackgroundThe long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out.MethodsTo optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours, Matrigel was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229) and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation.ResultsBoth human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay without permanent tumour control was obtained for both tumour entities.ConclusionThe already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental accelerators.
Highlights
Current state-of-the-art treatment of cancer patients most often includes radiotherapy with high energy photons or electrons that are delivered by compact clinical electron linear accelerators
The already established mouse ear tumour model was successfully upgraded providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental accelerators
For the FaDu model, tumour growth was explored in 162 mice after inoculation of 1Ã106 FaDu cells resolved in phosphate buffered saline (PBS) [10] or of 1Ã103–1Ã106 cells in pure (9.7 mg/ml) or diluted MG (1:1 dilution of Matrigel Basement Membrane Matrix, BD Biosciences, USA with PBS, Biochrom)
Summary
The long-term aim of developing laser based particle acceleration towards clinical application requires substantial technological progress, and the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out
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