Room: AAPM ePoster Library
Purpose: AGuIX is a clinically emerging theranostic agent comprised of gadolinium-based nanoparticles. It has been shown to localise in tumours, providing excellent MR contrast and enhancing patient response to radiotherapy. However, enhancement of radiation damage by AGuIX exceeds that predicted by standard models based on macroscale dose enhancement. AGuIX is designed so that all gadolinium atoms are located at the nanoparticle surface. This unique geometry may allow Auger cascades from one gadolinium atom to excite neighbouring atoms, leading to further amplification of the Auger cascade. This study aims to simulate the radio-enhancement effects of AGuIX, highlighting those that are purely geometric in origin.
Methods: Monte Carlo simulations using TOPAS were performed to investigate the radio-enhancement effects of AGuIX in water when irradiated by a 51 keV photon beam, compared to a homogeneous, spherical nanoparticle of identical elemental composition. The two geometries were compared by examining, relative to water, absolute dose enhancement ratio (DER) and nano-Radio Enhancement Ratio (nano-RER), defined as the ratio of the number of secondary electrons produced with/without the nanoparticle present. Relative DER and nano-RER for AGuIX compared to the homogeneous nanoparticle was also measured.
Results: DER was greater within 1,000 nm of AGuIX compared to the homogeneous nanoparticle. Relative DER was up to 66% higher, with absolute DER being up to 190 times higher. AGuIX released 30% more secondary electrons per primary photon ionisation, resulting in relative nano-RER over 10% greater within 300 nm of the nanoparticle, with absolute nano-RER up to 20 times greater.
Conclusion: Monte Carlo simulations demonstrated that AGuIX’s unique geometry is a key determining factor in its performance as a radio-enhancer when compared to a homogeneous nanoparticle. The radio-enhancement can be attributed to dose heterogeneity, with intense, localised, nanoscale damage produced near the AGuIX nanoparticles as a result of Auger cascades from gadolinium.
Funding Support, Disclosures, and Conflict of Interest: This work was supported by the Cancer Institute NSW/Translational Program Grant: Cancer imaging and targeted radiation therapy: Innovation, discovery and translation.
Auger Electrons, Contrast Agent, Monte Carlo