Influence of radiotherapy dose rate on gold nanoparticle-induced radiosensitization from high dose-rate brachytherapy
Daniel Cecchi1, Nolan Jackson1, Sacha Freeman1
1Department of Physics and Astronomy, University of Victoria, Victoria, British Columbia, Canada.
Background:
Associated normal tissue toxicity from current radiotherapy (RT) treatments limits effective dose escalation in the tumor to achieve nominal treatment results. Gold nanoparticles (GNPs) as radiosensitizing agents to locally increase photoelectron production have gained interest as a safe and viable method to improve therapeutic results. Among many other factors, the dose rate of the incident radiation has been shown to affect the radiosensitizing properties of GNPs significantly.
Purpose:
To evaluate GNP-induced radiosensitization during variable dose rate delivery from the decay of a high dose rate brachytherapy 192-Ir source and a clinical 6MV linear accelerator (LINAC).
Methods:
HEC-1A endometrial cancer cells were seeded into 35mm petri dishes with or without 10µg/mL with spherical 11nm GNPs functionalized with polyethylene glycol and integrin binding domain RGD to improve intracellular uptake. Variable dose rate delivery from the 192-Ir source was achieved at two source strengths of 37.95 mGy m2/h and 18.97 mGy m2/h, corresponding to dose rates of 1.1 and 0.55Gy/min, respectively. For 6MV irradiations, dose rate variability was controlled by adjusting the distance to the target from 91cm to 129cm, yielding identical dose rates of 1.1 and 0.55Gy/min, respectively. Cellular viability was measured using a clonogenic assay after irradiations between 0 and 8Gy, and a DNA double-strand break assay after 2Gy irradiations.
Results:
GNP-induced radiosensitization was significantly greater with higher dose rates than lower. Clonogenic loss with GNPs was increased from 1.00 to 1.19 (p < 0.001) with higher dose rates from 192-Ir source and from 1.03 to 1.16 (p < 0.001) with higher dose rate LINAC irradiations. DNA damage increase from GNPs was not significant at lower dose rates for both 192-Ir (p > 0.05) and LINAC (p > 0.05) irradiations; however, DNA damage was significantly increased at higher dose rates (192-Ir: p < 0.01; 6MV: p < 0.05).
Conclusions:
We have successfully demonstrated in vitro that clinically plausible GNP concentrations can induce variable radiosensitization based on the administered dose rate from both 192-Ir and LINAC irradiations. This work demands future research into the clinical translation of GNPs into high-dose-rate environments.
