The dosimetric feasibility of gold nanoparticle-aided radiation therapy (GNRT) via brachytherapy using low-energy gamma-/x-ray sources

Abstract

The preferential accumulation of gold nanoparticles within tumors and the increased photoelectric absorption due to the high atomic number of gold cooperatively account for the possibility of significant tumor dose enhancement during gold nanoparticle-aided radiation therapy (GNRT). Among the many conceivable ways to implement GNRT clinically, a brachytherapy approach using low-energy gamma-/x-ray sources (i.e. E(avg) < 100 keV) appears to be highly feasible and promising, because it may easily fulfill some of the technical and clinical requirements for GNRT. Therefore, the current study investigated the dosimetric feasibility of implementing GNRT using the following sources: (125)I, 50 kVp and (169)Yb. Specifically, Monte Carlo (MC) calculations were performed to determine the macroscopic dose enhancement factors (MDEF), defined as the ratio of the average dose in the tumor region with and without the presence of gold nanoparticles during the irradiation of the tumor, and the photo/Auger electron spectra within a tumor loaded with gold nanoparticles. The current study suggests that a significant tumor dose enhancement (e.g. >40%) could be achievable using (125)I, 50 kVp and (169)Yb sources and gold nanoparticles. When calculated at 1.0 cm from the center of the source within a tumor loaded with 18 mg Au g(-1), macroscopic dose enhancement was 116, 92 and 108% for (125)I, 50 kVp and (169)Yb, respectively. For a tumor loaded with 7 mg Au g(-1), it was 68, 57 and 44% at 1 cm from the center of the source for (125)I, 50 kVp and (169)Yb, respectively. The estimated MDEF values for (169)Yb were remarkably larger than those for (192)Ir, on average by up to about 70 and 30%, for 18 mg Au and 7 mg Au cases, respectively. The current MC study also shows a remarkable change in the photoelectron fluence and spectrum (e.g. more than two orders of magnitude) and a significant production (e.g. comparable to the number of photoelectrons) of the Auger electrons within the tumor region due to the presence of gold nanoparticles during low-energy gamma-/x-ray irradiation. The radiation sources considered in this study are currently available and tumor gold concentration levels considered in this investigation are deemed achievable. Therefore, the current results strongly suggest that GNRT can be successfully implemented via brachytherapy with low energy gamma-/x-ray sources, especially with a high dose rate (169)Yb source.

Figure 1

X-ray spectrum for a 50 kVp x-ray source (1.5 mm Al filter, 17° W target). Spectral data are obtained from Birch et al (1979).

Figure 2

Total photon interaction cross-sections for various materials considered in this study. The data are obtained using XCOM software (Berger et al 2005). The photon absorption edges for gold-loaded tissues become pronounced in this figure as the amount of gold within the ICRU tissue increases.

Figure 3

The calculated macroscopic dose enhancement factor (MDEF) for ¹²⁵I cases as a function of radial distance along the transverse axis of the source. The factors shown from r = 2 to 10 cm are not the MDEFs but show the decrease in the doses behind the tumor loaded with gold nanoparticles. The radius of a spherical tumor centered at the origin is 1.5 cm. The statistical uncertainty (1σ) of each data point is comparable to the size of the symbols. The amount of gold shown in the figure legend is per gram of tumor or tissue.

Figure 4

The calculated macroscopic dose enhancement factor (MDEF) for 50 kVp cases as a function of radial distance along the transverse axis of the phantom. The factors shown from r = 2 to 10 cm are not the MDEFs but show the decrease in the doses behind the tumor loaded with gold nanoparticles. The radius of a spherical tumor centered at the origin is 1.5 cm. The statistical uncertainty (1σ) of each data point is comparable to the size of the symbol. The amount of gold shown in the figure legend is per gram of tumor or tissue.

Figure 5

The calculated macroscopic dose enhancement factor (MDEF) for ¹⁶⁹Yb cases as a function of radial distance along the transverse axis of the source. The ¹⁹²Ir results obtained from a previous study (Cho 2005) are also shown in this figure. If less than unity, the factors shown from r = 4 to 10 cm are not the MDEFs but show the decrease in the doses behind the tumor loaded with gold nanoparticles. The radius of a spherical tumor centered at the origin is 3.5 cm. The statistical uncertainty (1σ) of each data point is comparable to the size of the symbol. The amount of gold shown in the figure legend is per gram of tumor or tissue.

Figure 6

Photoelectron spectra within a 3 × 3 × 3 cm³ tumor irradiated by ¹²⁵I gamma rays from a source located at the center of the tumor. The spectra are shown for a tumor loaded with gold nanoparticles at 7 mg g⁻¹ and for a tumor without gold nanoparticles.

Figure 7

Photoelectron spectra within a 3 × 3 × 3 cm³ tumor irradiated by 50 kVp x-rays from a source located at the center of the tumor. The spectra are shown for a tumor loaded with gold nanoparticles at 7 mg g⁻¹ and for a tumor without gold nanoparticles.

Figure 8

Photoelectron spectra within a 3 × 3 × 3 cm³ tumor irradiated by ¹⁶⁹Yb gamma rays from a source located at the center of the tumor. The spectra are shown for a tumor loaded with gold nanoparticles at 7 mg g⁻¹ and for a tumor without gold nanoparticles.

Figure 9

Auger electron spectra within a 3 × 3 × 3 cm³ tumor irradiated by ¹²⁵I, 50 kVp and ¹⁶⁹Yb sources located at the center of the tumor. The spectra are shown only for a tumor loaded with gold nanoparticles at 7 mg g⁻¹, because Auger electrons above 1 keV are not seen for a tumor without gold nanoparticles. No distinction between the Auger and Coster-Kronig electrons is made for these spectra.