Purpose: The authors describe a method in which fluorescence nuclear track detectors (FNTDs), novel track detectors with nanoscale spatial resolution, are used to determine the linear energy transfer (LET) of individual proton tracks from proton therapy beams by allowing visualization and 3D reconstruction of such tracks. Methods: FNTDs were exposed to proton therapy beams with nominal energies ranging from 100 to 250 MeV. Proton track images were then recorded by confocal microscopy of the FNTDs. Proton tracks in the FNTD images were fit by using a Gaussian function to extract fluorescence amplitudes. Histograms of fluorescence amplitudes were then compared with LET spectra. Results: The authors successfully used FNTDs to register individual proton tracks from high-energy proton therapy beams, allowing reconstruction of 3D images of proton tracks along with delta rays. The track amplitudes from FNTDs could be used to parameterize LET spectra, allowing the LET of individual proton tracks from therapeutic proton beams to be determined. Conclusions: FNTDs can be used to directly visualize proton tracks and their delta rays at the nanoscale level. Because the track intensities in the FNTDs correlate with LET, they could be used further to measure LET of individual proton tracks. This method may be useful for measuring nanoscale radiation quantities and for measuring the LET of individual proton tracks in radiation biology experiments. C
Purpose To show that intrinsic radiosensitivity varies greatly for protons and carbon (C) ions in addition to photons, and that DNA repair capacity remains important in governing this variability. Methods We measured or obtained from the literature clonogenic survival data for a number of human cancer cell lines exposed to photons, protons (9.9 keV/μm), and C‐ions (13.3–77.1 keV/μm). We characterized their intrinsic radiosensitivity by the dose for 10% or 50% survival (D10% or D50%), and quantified the variability at each radiation quality by the coefficient of variation (COV) in D10% and D50%. We also treated cells with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability. Results We found no statistically significant differences in the COVs of D10% or D50% between any of the radiation qualities investigated. The same was true regardless of whether the cells were treated with DNA repair inhibitors, or whether they were stratified into histologic subsets. Even within histologic subsets, we found remarkable differences in radiosensitivity for high LET C‐ions that were often greater than the variations in RBE, with brain cancer cells varying in D10% (D50%) up to 100% (131%) for 77.1 keV/μm C‐ions, and non‐small cell lung cancer and pancreatic cancer cell lines varying up to 55% (76%) and 51% (78%), respectively, for 60.5 keV/μm C‐ions. The cell lines with modulated DNA repair capacity had greater variability in intrinsic radiosensitivity across all radiation qualities. Conclusions Even for cell lines of the same histologic type, there are remarkable variations in intrinsic radiosensitivity, and these variations do not differ significantly between photon, proton or C‐ion radiation. The importance of DNA repair capacity in governing the variability in intrinsic radiosensitivity is not significantly diminished for higher LET radiation.
PurposeHigh energetic carbon (C‐) ion beams undergo nuclear interactions with tissue, producing secondary nuclear fragments. Thus, at depth, C‐ion beams are composed of a mixture of different particles with different linear energy transfer (LET) values. We developed a technique to enable isolation of DNA damage response (DDR) in mixed radiation fields using beam line microscopy coupled with fluorescence nuclear track detectors (FNTDs).MethodsWe imaged live cells on a coverslip made of FNTDs right after C‐ion, proton or photon irradiation using an in‐house built confocal microscope placed in the beam path. We used the FNTD to link track traversals with DNA damage and separated DNA damage induced by primary particles from fragments.ResultsWe were able to spatially link physical parameters of radiation tracks to DDR in live cells to investigate spatiotemporal DDR in multi‐ion radiation fields in real time, which was previously not possible. We demonstrated that the response of lesions produced by the high‐LET primary particles associates most strongly with cell death in a multi‐LET radiation field, and that this association is not seen when analyzing radiation induced foci in aggregate without primary/fragment classification.ConclusionsWe report a new method that uses confocal microscopy in combination with FNTDs to provide submicrometer spatial‐resolution measurements of radiation tracks in live cells. Our method facilitates expansion of the radiation‐induced DDR research because it can be used in any particle beam line including particle therapy beam lines.CategoryBiological Physics and Response Prediction.
Purpose:To develop an empirical model to predict radiosensitivity and relative biological effectiveness (RBE) after helium (He) and carbon (C) ion irradiation with or without DNA repair inhibitors. Methods: We characterized survival in eight human cancer cell lines exposed to 6 MV photons and to He-and C-ions with linear energy transfer (LET) values of 2.2-60.5 keV/µm to verify that the radiosensitivity parameters (D5%, D10%, D20%, D37%, D50% and SF2Gy) correlate linearly between photon and ion radiation with or without DNA-PKcs or ATR inhibitors. Then, we parameterized the LET response of the parameters governing these linear correlations up to LET values of 225 keV/μm using the data in the Particle Irradiation Data Ensemble (PIDE) v3.2 database, creating a model that predicts a cell's ion radiosensitivity, RBE and ion survival curve for a given LET on the basis of the cell's photon radiosensitivity. We then trained this model using the PIDE database as a training dataset, and validated it by predicting the radiosensitivity of the cell lines we exposed to He-and C-ions with LET ranging from 2.2-60.5 keV/μm. Results: Radiosensitivity to ions depended linearly with radiosensitivity of photons in the range of investigated LET values and the slopes and intercepts of these linear relationships within the PIDE database vary exponentially and linearly, respectively. Our model predicted ion radiosensitivity (e.g., D10%) within 5.1-21.3%, RBED10% within 5.0-17.1%, and ion mean inactivation dose within 6.7-25.1% for He-and C-ion LET ranging from 2.2-60.5 keV/µm. Conclusions: Radiosensitivity to He-and C-ions depend linearly with radiosensitivity to photons and can be used to predict ion radiosensitivity, RBE and cell survival curves for clinically relevant LET values from 2.2-60.5 keV/µm, with or without drug treatment. SUMMARYWe present a new empirical model capable of predicting clonogenic cell survival of cell lines exposed to helium and carbon ion beams. Our model is based on an observed linear correlation between radiosensitivity to ions and photons across a wide range of LET values. This linear correlation can be used to predict ion RBE, radiosensitivity, and the cell survival curve for a given LET all based on a cell's photon survival curve.
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