Experimental Evaluation of Free Radical Generation in Nanoparticle-Aided Radiation Therapy
N Paudel*, D Shvydka, E Findsen, E Parsai, University of Toledo, Toledo, OHSU-E-T-341 Sunday 3:00PM - 6:00PM Room: Exhibit Hall
Purpose: Use of gold nanoparticles (NPs) in radiation therapy has been found promising due to the possibility of selective radiation dose enhancement within a tumor, and favorable biological compatibility. Recent studies demonstrated that the biological effect exceeds the expectations based on the physical energy deposition solely, thus pointing toward biochemical factors. Since free radicals are responsible for the majority of the biological damage, evaluation of their radiation induced free radicals near the gold-tissue interface offers a more relevant estimate of the biological damage in NP-aided radiation treatments.
Methods: Samples in the capillaries were irradiated with clinical Ir-192 HDR source. Since free radicals are very short-lived (~nanoseconds), we used a spin trap agent, high purity DMPO dissolved in water, to trap hydroxyl radicals generated by radiolysis of water. The formed spin adducts retain spin properties of free radicals for a prolonged time (~hours), especially at low temperatures. Radicals were detected via electron spin resonance (ESR) spectrometry technique. Quantification of free radicals generated in water and in the presence of a thin gold wire was done by double integration of the obtained spectra.
Results: Our Monte Carlo simulations demonstrated that the dose enhancement region is limited to a close vicinity (less than 1mm) of the gold-tissue interface still suitable for free radical measurement with ESR spectroscopy. We have established a protocol for quantitative ESR measurements. The radical generation was found to be proportional to the radiation dose, and strongly enhanced by the presence of gold.
Conclusions: Free radicals generated by radiolysis of water can be measured quantitatively with ESR technique. Our evaluation of radiation induced free radical generation in water with nanoparticles sheds some light on the effects of NPs in biological systems.
Funding Support, Disclosures, and Conflict of Interest: This project is supported through an NRC grant for faculty development. It is grant number NRC-HQ-12-G-38-0042.