1. Methods & Materials (continued)
Measurements of gold nanoparticle-mediated proton dose enhancement due to particle-induced x-ray emission and activation products using radiochromic films and HPGe detector
J. Cho1, N. Manohar1,2, C. Gonzalez-Lepera3, M. Kerr1, S. Krishnan4, and S. H. Cho1
1 Dept of Radiatio 1 Department of Radiation Physics, 3 Nuclear Medicine, 4 Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
2 Department of Nuclear and Radiological Engineering and Medical Physics, Georgia Institute of Technology, Atlanta, GA
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 x-ray/gamma-ray emission (PIXE/PIGE) from GNPs,
Secondary electrons from GNPs due to proton-Au interactions,
Particle-induced nuclear activation products,
Reactive oxygen species (or free radicals), and
Pharmaco-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.
Results
Methods & Materials (continued)
Fig. 3: After proton irradiation, EBT2 films were removed from vials, wiped clean of residual GNPs and dried. Films were digitized for OD and dose calculation. For each tested dose and vial location, dose enhancement due to GNPs was calculated by taking the ratio of the dose measured in films immersed in the GNP solution to that in water only.
Fig. 6: Ratio of delivered dose between films immersed in GNP solutions (0.3 mg Au/g) and water. Samples receiving 6 Gy were located at 3 different depths (COM, COM ± 3 cm), while samples receiving other doses were located at COM only. No significant dose enhancement was observed, considering the statistical uncertainty (± 2%) of film dosimetry. The average dose enhancement and standard deviation were and 0.020, respectively.
Methods & Materials
(a) (b)
Fig. 1: (a) EBT2 films (bottom) were immersed in 1.8-mL vials containing: (left) water and GNPs (0.3 mg Au/g) and (right) water only. (b) Schematic diagram of vials with immersed EBT2 films.
Fig. 4: Schematic diagram of EBT2 film immersed in vials with GNPs. The active substrate layer is separated from the GNPs by 80 and 175 µm. The dose enhancement recorded in active substrate layer is from PIXE/PIGE-related photo/Auger electrons and other secondary electrons created from GNPs with ranges >80 µm. Shorter-ranged electrons are absorbed in the outer layers.
Fig. 7: Gamma counting performed for 45 hr after 1-hr post-irradiation delay. Spectral peaks from multiple radioisotopes created from proton-water (511 keV only) and proton-Au nuclear interactions were identified. Although only gamma and x-rays were counted, simultaneous electron emission was accounted for, when calculating dose enhancement due to activation products. Dose enhancement due to Au-originated activation products was minimal (<0.1%) when both proton-Au and secondary neutron-Au interactions were considered. Dose enhancement due to PIGE from GNPs was also found to be less than 0.1%, based on cross-section data.
Conclusion
In the current experiments, photons originating from GNPs due to PIXE/PIGE contributed minimally to dose enhancement. The secondary electrons from proton-Au interactions appeared to have made insignificant contributions to dose enhancement beyond 80 µm. This observation is in agreement with the latest Monte Carlo results demonstrating a highly localized (<100 nm) dose enhancement due to proton irradiation. The current investigation also suggests negligible dose enhancement due to activation products.
Fig. 2: The EBT2 film-containing vials were located at COM, COM + 3 cm, and COM - 3 cm and irradiated with 2, 4, 6, 8, and 10 Gy. 10 cm SOBP 160 MeV proton beam was used. A concentration of 0.3 mg Au/g was used to compare with in-vitro and animal experiments performed using the same concentration. A separate vial with a higher concentration of GNPs (20 mg Au/g) was irradiated at COM using 10 Gy to measure activation products (radioisotopes) from proton-Au nuclear interactions.
Fig. 5: Proton-irradiated GNP solution (20 mg Au/g) were pipetted to a clean vial that was not irradiated. The GNPs in the clean vial were placed in a 4π wall-type HPGe (high-purity germanium) detector for gamma spectrometry. Counting was started 9 min post-irradiation and performed for 5, 5, 10, 20 min and 45 hr in a consecutive order.
Supported in part by NIH/NCI grant R01CA155446