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Quantitative Characterization of Free Radical Generation Under High-Energy Photon Irradiation for Gold Nanoparticle Mediated Radiation Therapy

K Xie1*, A Ray2, D Shvydka1, E Parsai1, (1) University of Toledo Health Science Campus, Toledo, OH, (2) University Of Toledo Main Campus, Toledo, OH

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose:
We investigate the primary mechanism responsible for the tumoricidal effect of high-energy photon irradiation in the presence of gold nanoparticles (GNP) in aqueous media. Instead of the resultant physical dose enhancement, the effect is due to an increase in generation of reactive oxygen species (ROS) at the nanoparticle surface, acting as a catalyst. We develop and validate an approach to quantify the ROS generation through fluorescence spectroscopy.

Methods:
A compound containing 0.0005mg/ml concentration GNP solution (particle diameter 30nm, citrate coating) were mixed with anthracene derivative (Anthracene-9, 10-dipropionic acid disodium salt, a fluorescent molecule that is sensitive to ROS) dissolved in dimethyl sulfoxide. Samples were irradiated under Ir-192 HDR treatment source (average energy ~380keV). NaCl was added to samples after irradiation (concentration 1%w/v) in order to segregate nanoparticles at the bottom of glass capillaries. Fluorescence spectroscopy was performed on irradiated sample; the intensity of 430nm peak emitted by anthracene molecules was used to quantify the ROS generation. A Monte Carlo simulation of the experimental setup was also performed to compute the increase in dose deposition due to GNPs.

Results:
An experimental procedure for fluorescence spectroscopy was established and validated. In presence of ROS the signal intensity decreases due to rapid oxidation of the sensor molecule and we observe a signal intensity saturation at around 200Gy. The dose dependent change in fluorescence intensity shows the ROS yield in GNP sample was up to 110% higher than the control group (water alone). Analytical calculation, followed by Monte Carlo simulation (MCNP5) showed the dose enhancement in GNP solution is only 1.5% higher than in water.

Conclusion:
Free radicals generation by water radiolysis can be quantitatively characterized by fluorescence spectroscopy. Dose enhancement in aqueous media due to the presence of gold nanoparticle is vastly dominated by ROS production increase, mediating the biological response.

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