Volumetric Dose Enhancement Due to Time-Dependent Diffusion of Gold Nanoparticles Eluted from Loaded Spacers In Nanoparticle-Aided Brachytherapy
Abstract
Purpose
To investigate the time dependent distribution of gold nanoparticles released from a loaded brachytherapy spacer and the impact on the concomitant dose distribution in Iodine-125 low dose rate brachytherapy treatment.
Methods
A numerical method was developed to simulate the spatiotemporal evolution of 14 nm gold nanoparticles (GNP) concentration from eluting brachytherapy spacers in a tumor sub volume of 10x10x9.2 mm3. Four I-125 seeds and eluting spacers pairs were placed 2.5 mm apart in a grid with sources and spacers having opposite configurations to adjacent pairs and periodically mirrored in all three dimensions. The release rate was constant at 6.44 µg gold/day for 14 days and zero thereafter. This corresponds to 30 mg gold/g spacer load. The model also included a first-order approximation of nanoparticle removal due to endocytosis. The concentration distribution of gold nanoparticles was solved by employing a second-order finite difference scheme of the diffusion equation. The results were used to calculate the Dose Enhancement Factor (DEF) using linear interpolation of previous results. Using TG-43 formalism, dose from several Iodine-125 seeds was calculated with and without the nanoparticles using Air Kerma Strength (Sk).
Results
Results indicate that the elution rate used in this simulation yields a volume averaged DEF of 1.082, ranging between 1.063 and 1.235. An increase in dose homogeneity in regions between the sources was also observed. Using an initial Sk of 0.452 U with GNPs yields the same D90 as using an Sk of 0.500 U without GNPs, which represents a 9.6% smaller Sk.
Conclusion
The implementation of nanoparticle-eluting brachytherapy spacers allows for a more homogeneous dose distribution inside the tumor and can match the same clinical dose metrics with lower air-kerma strength seeds; thereby, improving normal tissue sparing. Further investigations into experimentally determined release patterns are warranted.