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A Mechanistic Model of Radiosensitization in the Presence of Metallic Nanoparticles


W Liu

H Yan1,2 , D Carlson2 , W Liu2*, (1) School of Biomedical Engineering, Capital Medical University, Beijing, China, 100069,(2) Yale Univ. School of Medicine, New Haven, CT

Presentations

TU-C2-GePD-T-1 (Tuesday, August 1, 2017) 10:00 AM - 10:30 AM Room: Therapy ePoster Lounge


Purpose: To model the radiosensitizing effect of Gold and Gadolinium nanoparticles (NPs) due to Auger electron cascade.

Methods: Similar to the repair-misrepair-fixation (RMF) model in the classification of inter- and intra-track DSB interactions, the damage caused by NP is divided into local part and non-local part. The local part contributes to the damage by acting like a bomb--when triggered by an ionization event, it releases a cascade of Auger electrons that cause lethal damage to the DNA at a probability when the NP is close to the DNA. The probability of lethal events depends on the number of photoelectric ionizations, the type and size of NPs and cells, and the X-ray spectrum. The non-local part due to the higher energy electrons released from an ionization in the NP contributes as regular sparsely distributed energy deposits. Monte Carlo simulations were carried out to estimate the ionization probabilities for 1.9 nm Gold NPs and 3.0 nm Gadolinium-based NPs, AGuIX. Emission of Auger electrons from interactions of 160/220 kVp X-rays and NPs in a cell was simulated. By estimating a lethal biological damage probability of the Auger electrons produced in an ionization event of the NP, we calculated α', the increase in α of the Linear-Quadratic survival model due to the NPs. The local lethal damage is proportional to dose therefore has no influence on β (D² term).

Results: α' due to 1.9 nm AuNPs at 2.5 mM Au for 160 kVp and 220 kVp irradiation is 0.17 and 0.082 Gy⁻¹, respectively; the corresponding α' due to 3.0 nm AGuIX at 0.68 mM Gd is 0.069 and 0.050 Gy⁻¹, respectively. These results are comparable to experimental data.

Conclusion: The NP radiosensitization effect, which cannot be explained by macroscopic dose enhancement, could be potentially explained using a bomb model of NP.


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