TU-H-CAMPUS-TeP3-01: Gold Nanoparticle-Enhanced Radiation Therapy in In Vitro A549 Lung Carcinoma: Studies in Both Traditional Monolayer and Three Dimensional Cell Culture Models

PURPOSE: To measure the increase in in vitro radiosensitivity for A549 lung carcinoma cells due to gold nanoparticle (GNP) radiation dose enhancement in both traditional monolayer and three dimensional (3D) cell culture models. METHODS: A γH2AX immunofluorescence assay is performed on monolayer A549 cell culture and quantitatively analyzed to measure the increase in double strand breaks (DSBs) resulting from GNP dose enhancement. A clonogenic survival assay (CSA) is then performed on monolayer A549 cell culture to assess true viability after treatment. And lastly, another γH2AX assay is performed on 3D A549 multicellular nodules overlaid on a bed of growth factor reduced matrigel to measure dose response in a model that better recapitulates treatment response to actual tumors in vivo. RESULTS: The first γH2AX assay performed on the monolayer cell culture shows a significant increase in DSBs due to GNP dose enhancement. The maximum average observed increase in normalized fluorescent intensity for monolayer cell culture is 171% for the 6Gy-treatment groups incubated in 0.556 mg Au/ml solution. The CSA performed on monolayer cell culture also shows considerable GNP dose enhancement. The maximum decrease in the normalized surviving fraction is 12% for the 4Gy-treatment group incubated in 0.556 mg Au/ml. And lastly, the GNP dose enhancement is confirmed to be mitigated in three dimensional cell culture models as compared to the traditional monolayer model. The maximum average observed dose enhancement for 3D cell culture is 19% for the 6Gy-treatment groups and incubated in 0.556 mg Au/ml. CONCLUSION: A marked increase in radiosensitivity is observed for A549 lung carcinoma cells when treated with GNPs plus radiation as opposed to radiation alone. Traditional monolayer cell culture also shows a much more pronounced radiation dose enhancement than 3D cell culture

Characterizing the Modulation Transfer Functions (MTFs) of Proton and Carbon Radiography Using GEANT4 Monte Carlo Simulations

Proton and carbon therapy are expanding in popularity as a clinical modality of external beam radiotherapy due to their finite range in tissue. However, patient setup, tumor tracking, and range uncertainties all continue to cause problems in delivering treatment. The development of proton/carbon radiography offers the potential to rectify all three of these problems. Imaging the patient immediately before (or even during) treatment would aid in patient setup and tumor tracking. Radiographs can also provide range information, which would reduce range uncertainties. Finally, both proton and carbon beams deliver a smaller absorbed dose to patients than their photon counterparts, when used to produce images. The aim of this study was to investigate the spatial resolution of both proton (230 MeV and 330 MeV) and carbon (400MeV/nucleon) radiography via monte carlo simulations. This was done for both cases by characterizing their modulation transfers functions (MTFs) and taking the 10% points. Our results indicate that both types of radiography yield sub-millimeter resolution and that carbon yields the better spatial resolution

Characterizing the modulation transfer function (MTF) of proton/carbon radiography using Monte Carlo simulations

Purpose: To characterize the modulation transfer function (MTF) of proton/carbon radiography using Monte Carlo simulations. To assess the spatial resolution of proton/carbon radiographic imaging. Methods: A phantom was specifically modeled with inserts composed of two materials with three different densities of bone and lung. The basic geometry of the phantom consists of cube-shaped inserts placed in water. The thickness of the water, the thickness of the cubes, the depth of the cubes in the water, and the particle beam energy have all been varied and studied. There were two phantom thicknesses considered 20 and 28 cm. This represents an average patient thickness and a thicker sized patient. Radiographs were produced for proton beams at 230 and 330 MeV and for a carbon ion beam at 400 MeV per nucleon. The contrast-to-noise ratio (CNR) was evaluated at the interface of two materials on the radiographs, i.e., lung-water and bone-water. The variation in CNR at interface between lung-water and bone-water were study, where a sigmoidal fit was performed between the lower and the higher CNR values. The full width half-maximum (FWHM) value was then obtained from the sigmoidal fit. Ultimately, spatial resolution was defined by the 10% point of the modulation-transfer-function (MTF 10%), in units of line-pairs per mm (lp/mm). Results: For the 20 cm thick phantom, the FWHM values varied between 0.5 and 0.7 mm at the lung-water and bone-water interfaces, for the proton beam energies of 230 and 330 MeV and the 400 MeV/n carbon beam. For the 28 cm thick phantom, the FWHM values varied between 0.5 and 1.2 mm at the lung-water and bone-water interface for the same inserts and beam energies. For the 20 cm phantom the MTF 10% for lung-water interface is 2.3, 2.4, and 2.8 lp/mm, respectively, for 230, 330, and 400 MeV/n beams. For the same 20 cm thick phantom but for the bone-water interface the MTF 10% yielded 1.9, 2.3, and 2.7 lp/mm, respectively, for 230, 330, and 400 MeV/n beams. In the case of the thicker 28 cm phantom, the authors observed that at the lung-water interface the MTF 10% is 1.6, 1.9, and 2.6 lp/mm, respectively, for 230, 330, and 400 MeV/n beams. While for the bone-water interface the MTF 10% was 1.4, 1.9, and 2.9 lp/mm, respectively, for 230, 330, and 400 MeV/n beams. Conclusions: Carbon radiography (400 MeV/n) yielded best spatial resolution, with MTF 10% = 2.7 and 2.8 lp/mm, respectively, at the lung-water and bone-water interfaces. The spatial resolution of the 330 MeV proton beam was better than the 230 MeV proton, because higher incident proton energy suffer smaller deflections within the patient and thus yields better proton radiographic images. The authors also observed that submillimeter resolution can be obtained with both proton and carbon beams