Recently, interactions of x-rays with gold nanoparticles (GNPs) and the resulting dose enhancement have been studied using several Monte Carlo (MC) codes (Jones et al 2010 Med. Phys. 37 3809-16, Lechtman et al 2011 Phys. Med. Biol. 56 4631-47, McMahon et al 2011 Sci. Rep. 1 1-9, Leung et al 2011 Med. Phys. 38 624-31). These MC simulations were carried out in simplified geometries and provided encouraging preliminary data in support of GNP radiotherapy. As these studies showed, radiation transport computations of clinical beams to obtain dose enhancement from nanoparticles has several challenges, mostly arising from the requirement of high spatial resolution and from the approximations used at the interface between the macroscopic clinical beam transport and the nanoscopic electron transport originating in the nanoparticle or its vicinity. We investigate the impact of MC simulation geometry on the energy deposition due to the presence of GNPs, including the effects of particle clustering and morphology. Dose enhancement due to a single and multiple GNPs using various simulation geometries is computed using GEANT4 MC radiation transport code. Various approximations in the geometry and in the phase space transition from macro- to micro-beams incident on GNPs are analyzed. Simulations using GEANT4 are compared to a deterministic code CEPXS/ONEDANT for microscopic (nm-µm) geometry. Dependence on the following microscopic (µ) geometry parameters is investigated: µ-source-to-GNP distance (µSAD), µ-beam size (µS), and GNP size (µC). Because a micro-beam represents clinical beam properties at the microscopic scale, the effect of using different types of micro-beams is also investigated. In particular, a micro-beam with the phase space of a clinical beam versus a plane-parallel beam with an equivalent photon spectrum is characterized. Furthermore, the spatial anisotropy of energy deposition around a nanoparticle is analyzed. Finally, dependence of dose enhancement on the number of GNPs in a finite cluster of nanoparticles is determined. Simulations were performed for 100 nm GNPs irradiated in water phantom by various monoenergetic (11 keV-1 MeV) and spectral (50 kVp) sources. The dose enhancement ratio (DER) is very sensitive to the specific simulation geometry (µSAD, µS, µC parameters) and µ-source type. For a single GNP the spatial distribution of DER is found to be nearly isotropic with limited magnitude and relatively short range (∼100-200 nm for DER significantly greater than 1). For a cluster of GNPs both the magnitude and range are found much greater (∼1-2 µm). The relation between DER for a cluster of GNPs and a single GNP is strongly nonlinear. Relatively strong dependence of DER on the simulation micro-geometry cautions future studies and the interpretation of existing MC results obtained in different simulations geometries. The nonlinear relation between DER for a single and multiple GNPs suggests that parameters such as the number of adjacent nanoparticles per cell and the distances between the GNPs and the cel...

This study determines the optimal clinical scenarios for gold nanoparticle dose enhancement as a function of irradiation conditions and potential biological targets using megavoltage x-ray beams. Four hundred and eighty clinical beams were studied for different potential cellular or sub-cellular targets. Beam quality was determined based on a 6 MV linac with and without a flattening filter for various delivery conditions. Dose enhancement ratios DER = D GNP /D water were calculated for all cases using the GEANT4 Monte Carlo code and the CEPXS/ONEDANT radiation transport deterministic code. Dose enhancement using GEANT4 agreed with CEPXS/ONEDANT. DER for unflattened beams is ∼2 times larger than for flattened beams. The maximum DER values were calculated for split-IMRT fields (∼6) and for out-of-field areas of an unflattened linac (∼17). In-field DER values, at the surface of gold nanoparticles, ranged from 2.2 to 4.2 (flattened beam) and from 3 to 4.7 (unflattened beams). For a GNP cluster with thicknesses of 10 and 100 nm, the DER ranges from 14% to 287%. DER is the greatest for split-IMRT, larger depths, out-of-field areas and/or unflattened linac. Mapping of a GNP location in tumor and normal tissue is essential for efficient and safe delivery of nanoparticle-enhanced radiotherapy.

AGuIX are gadolinium-based nanoparticles developed mainly for imaging due to their MR contrast properties. They also have a potential role in radiation therapy as a radiosensitizer. We used MRI to quantify the uptake of AGuIX in pancreatic cancer cells, and TEM for intracellular localization. We measured the radiosensitization of a pancreatic cancer cell line in a low-energy (220 kVp) beam, a standard 6 MV beam (STD) and a flattening filter free 6 MV beam (FFF). We demonstrated that the presence of nanoparticles significantly decreases cell survival when combined with an X-ray beam with a large proportion of low-energy photons (close to the k-edge of the nanoparticles). The concentration of nanoparticles in the cell achieves its highest level after 15 min and then reaches a plateau. The accumulated nanoparticles are mainly localized in the cytoplasm, inside vesicles. We found that the 6 MV FFF beams offer the best trade-off between penetration depth and proportion of low-energy photons. At 10 cm depth, we measured a DEF20 % of 1.30 ± 0.47 for the 6 MV FFF beam, compared to 1.23 ± 0.26 for the 6 MV STD beam. Additional measurements with un-incubated nanoparticles provide evidence that chemical processes might also be contributing to the dose enhancement effect.

The aim of this study is twofold: (a) determination of the spectral differences for flattening-filter-free (FFF) versus standard (STD) linac under various clinical conditions, (b) based on an extensive list of clinically important beam configurations, identification of clinical scenarios that lead to higher macroscopic dose perturbations due to the presence of high-Z material. The focus is on dose enhancement due to contrast agents including high-Z elements such as gold or gadolinium. EGSnrc was used to simulate clinical beams under various irradiation conditions: open/IMRT/spit-IMRT fields, in/out-off-field areas, different depths and field sizes. Spectra were calculated and analyzed for about 80 beams and for a total of 480 regions. Quantitative differential effects in beam quality were characterized using energy-dependent and cumulative dose perturbation metrics. Analysis of the spectral database showed that even though the general trends for both linacs (FFF/STD) were the same, there were crucial differences. In general, the relative changes between different conditions were smaller for FFF spectra. This was because of the higher component of low-energy photons of the FFF linac, which already lead to higher dose enhancement than for the STD linac (photon energies were more "uniformly" distributed for FFF spectra and henceforth their perturbation resulted in lesser relative changes). For out-of-field FFF spectra and split-IMRT fields the strongest enhancement were observed (∼25 and ∼5 respectively). Different spectral scenarios lead to different dose enhancements, however, they scale with the higher effective-Z of the materials and were directly related to the lower range of the spectra (<200 keV).

A modified FFF beamline with increased energy and electron beam angular spread results in satisfactory flattened beam and high dose rate within the field. Peripheral dose remaining at similar (or smaller) level than that of STD linac for the same delivered dose within the treatment field.

We predict, for the first time, that by using United States Food and Drug Administration approved concentrations of cisplatin, major radiosensitization may be achieved via photoelectric mechanism during concomitant chemoradiotherapy (CCRT). Our analytical calculations estimate that radiotherapy (RT) dose to cancer cells may be enhanced via this mechanism by over 100% during CCRT. The results proffer new potential for significantly enhancing CCRT via an emerging clinical scenario, where the cisplatin is released in-situ from RT biomaterials loaded with cisplatin nanoparticles.

The presented stochastic framework can be used in interpretation of experimental cell survival or tumor control probability studies.

Low-Z (2.5 MV) GNPT is possible even after accounting for greater beam attenuation for deep-seated tumors (22 cm) and the increased skin dose. Further, it can lead to significant sparing of normal tissue while simultaneously escalating the dose in the tumor cells.