Targeted radiotherapy enhancement during electronic brachytherapy of accelerated partial breast irradiation (APBI) using controlled release of gold nanoparticles.

Several studies have demonstrated low rates of local recurrence with brachytherapy-based accelerated partial breast irradiation (APBI). However, long-term outcomes on toxicity (e.g. telangiectasia) and cosmesis remain a major concern. The purpose of this study is to investigate the dosimetric feasibility of using targeted non-toxic radiosensitizing gold nanoparticles (GNPs) for localized dose enhancement to the planning target volume (PTV) during electronic brachytherapy APBI while reducing normal tissue toxicity. We propose to incorporate GNPs into a micrometer-thick polymer film on the surface of routinely used lumpectomy balloon applicators and provide subsequent treatment using a 50 kVp Xoft device. An experimentally determined diffusion coefficient was used to determine space-time customizable distribution of GNPs for feasible in-vivo concentrations of 7 mg/g and 43 mg/g. An analytical approach from previously published work was employed to estimate the dose enhancement due to GNPs as a function of distance up to 1 cm from the lumpectomy cavity surface. Clinically significant dose enhancement values of at least 1.2, due to 2 nm GNPs, were found at 1 cm away from the lumpectomy cavity wall when using electronic brachytherapy APBI. Higher customizable dose enhancement was also achieved at other distances as a function of nanoparticle size. Our preliminary results suggest that significant dose enhancement can be achieved to residual tumor cells targeted with GNPs during APBI with electronic brachytherapy.

Low-Z linac targets for low-MV gold nanoparticle radiation therapy.

PURPOSE: To investigate the potential of low-Z/low-MV (low-Z) linac targets for gold nanoparticle radiotherapy (GNPT) and to determine the microscopic dose enhancement ratio (DER) due to GNP for the alternative beamlines. In addition, to evaluate the degradation of dose enhancement arising from the increased attenuation of x rays and larger skin dose in water for the low-MV beams compared to the standard linac. METHODS: Monte Carlo simulations were used to compute dose and DER for various flattening-filter-free beams (2.5, 4, 6.5 MV). Target materials were beryllium, diamond, and tungsten-copper high-Z target. Target thicknesses were selected based on 20%, 60%, 70%, and 80% of the continuous slowing down approximation electron ranges for a given target material and energy. Evaluation of the microscopic DER was carried out for 100 nm GNP including the degradation factors due to beam attenuation. RESULTS: The greatest increase in DER compared to the standard 6.5 MV linac was for a 2.5 MV Be-target (factor of ∼ 2). Skin dose ranged from ∼ 10% (Be, 6.5 MV-80%) to ∼ 85% (Be, 2.5 MV-20%) depending on the target case. Attenuation of 2.5 MV beams at 22 cm was higher by ∼ 75% compared with the standard beam. Taking into account the attenuation at 22 cm depth, the effective dose enhancement was up to ∼ 60% above the DER of the high-Z target. For these cases the effective DER ranged between ∼ 1.6 and 6 compared with the standard linac. CONCLUSIONS: 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.

Beam quality and dose perturbation of 6 MV flattening-filter-free linac.

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).