WE-G-BRE-02: Biological Modeling of Gold Nanoparticle Radiosensitization for Proton Therapy

Abstract

Purpose: The aim of this work is to investigate the radiosensitization effect of gold nanoparticles (GNP) in a proton beam. A computational model was built using the Local Effect Model (LEM) to predict the biological outcome of gold nanoparticle (GNP) sensitization. We present the results using a clinical proton beam, 6MV photon beam and two kilovoltage photon beams. Methods: First, Monte Carlo simulations were carried out using TOPAS (TOol for PArticle Simulation) to obtain the spatial dose distribution in the vicinity of GNPs. The dose distribution was then used as an input for LEM, which predicts dose-response curves for high linear energy transfer radiation using the track structure. The cell survival curves were evaluated for three particle sources (proton beam, MV photon beam and kV photon beam), various treatment depths for each particle source, various GNP uptakes and two different GNP sizes. Results: For proton therapy, the GNP sensitization effect is highly dependent on the treatment depth due to the energy-dependent interaction probability. We predict that if GNPs can be taken up by the cell nucleus, proton therapy can be significantly enhanced. If GNPs are only internalized into the cytoplasm, proton therapy can still be enhanced by GNPs and if GNPs are not internalized into cells, there will be no direct damage to the nucleus. For the same GNP uptake and concentration, the cell survival at 2Gy is reduced by 80% using kilovoltage photons, 50% using protons and only 2% using clinical MV photons. Finally, for the same weight of GNPs taken up by the cells, 10 nm GNPs causes 3 times more damage than 50 nm GNPs. Conclusion: We showed that GNPs have potential to be used to enhance radiation therapy for clinical proton beams.