Abstract

Purpose: There have been several reports of enhanced cell-killing and tumor regression when tumor cells and mouse tumors were loaded with gold nanoparticles (GNPs) prior to proton irradiation. While particle-induced xray emission (PIXE), Auger electrons, secondary electrons, free radicals, and biological effects have been suggested as potential mechanisms responsible for the observed GNP-mediated dose enhancement/radiosensitization, there is a lack of quantitative analysis regarding the contribution from each mechanism. Here, we report our experimental effort to quantify some of these effects. Methods: 5-cm-long cylindrical plastic vials were filled with 1.8 mL of either water or water mixed with cylindrical GNPs at the same gold concentration (0.3 mg Au/g) as used in previous animal studies. A piece of EBT2 radiochromic film (30-µm active-layer sandwiched between 80/175-µm outer-layers) was inserted along the long axis of each vial and used to measure dose enhancement due to PIXE from GNPs. Vials were placed at center-of-modulation (COM) and 3-cm up-/down-stream from COM and irradiated with 5 different doses (2–10 Gy) using 10-cm-SOBP 160-MeV protons. After irradiation, films were cleaned and read to determine the delivered dose. A vial containing spherical GNPs (20 mg Au/g) was also irradiated, and gamma-rays from activation products were measured using a cadmium-telluride (CdTe) detector. Results: Film measurements showed no significant dose enhancement beyond the experimental uncertainty (∼2%). There was a detectable activation product from GNPs, but it appeared to contribute to dose enhancement minimally (<0.01%). Conclusion: Considering the composition of EBT2 film, it can be inferred that gold characteristic x-rays from PIXE and their secondary electrons make insignificant contribution to dose enhancement. The current investigation also suggests negligible dose enhancement due to activation products. Thus, previously-reported GNP-mediated proton dose enhancement/radiosensitization needs to be attributed to one or more of the other mechanisms listed earlier. Supported in part by NIH/NCI grant R01CA155446;This investigation was supported in part by NIH/NCI grant R01CA155446.

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