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Assessing the Effect of Cell Geometry On Gold Nanoparticle Radiosensitization with Monte Carlo Track Structure Simulations

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A McNamara

A McNamara1*, W Sung2 , S McMahon3 , J Ramos-Mendez4 , J Perl5 , B Faddegon4 , K Held1 , H Paganetti1 , J Schuemann1 , (1) Massachusetts General Hospital & Harvard Med. Sch., Boston, MA, (2) Seoul National University, Suwon, ,(3) Queen's University, Belfast, Belfast, Co. Down, (4) University of California San Francisco, San Francisco, CA, (5) Stanford Linear Accelerator Center, Menlo Park, CA


SU-F-FS1-4 (Sunday, July 30, 2017) 2:05 PM - 3:00 PM Room: Four Seasons 1

Purpose: Gold nanoparticle (GNP) radiosensitization has been observed both in vitro and in vivo for kV x-ray irradiation. In this study we aim to assess the biological effectiveness of GNPs distributed in the extracellular media for realistic 3D cell geometries, using track structure Monte Carlo simulations, by calculating the cell survival fraction.

Methods: The radiobiological Monte Carlo simulation toolkit, TOPAS-nBio was used to simulate the track structure of photon trajectories through the cell geometry. GNPs were distributed randomly in the extracellular media with a mass concentration of 2%. Different cellular geometries were modeled and different nucleus positions were considered for each cell type. The number of single and double strand breaks occurring in the nucleus was calculated using a density-based spatial clustering of applications with noise (DBSCAN) algorithm and the number of lethal events was inferred for each case. The cell survival fraction was calculated for each of the geometric cases and compared to a 2D analytical calculation based on the local effect model (LEM).

Results: The results show that radiosensitization of the cell is highly dependent on the cell geometry. Both the MC and analytical calculations show that cells with a nucleus located close to the membrane have the greatest radiosensitization from GNPs located in the extracellular media. The track structure simulations predict lower survival fractions than the 2D analytical calculation especially at doses greater than 4 Gy, indicating that the full effect of the GNPs is not accounted for in the 2D calculation.

Conclusion: Our results show that GNP radiosensitization can be achieved for kV photons, even without cellular uptake of GNPs, when the nucleus is shifted towards the cell membrane. Track structure simulations with a 3D model shows promise to more accurately predict the biological effect from GNPs.

Funding Support, Disclosures, and Conflict of Interest: This work was supported by the National Institutes of Health (NIH)/National Cancer Institute (NCI) grant R01 CA187003.

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