Background: Auger cascades generated in high atomic number nanoparticles (NPs) following an ionization were considered as a potential mechanism for the NP radiosensitization. The Auger electrons have short ranges and can locally damage tumor cells, resulting in larger biological effect than radiation alone.
Aim: In this work, we investigated the microdosimetric
consequences of the Auger cascade using the theory of dual radiation action
(TDRA) and proposed a novel Bomb model as a general framework for describing
NP-related radiosensitization. When triggered by an ionization event, the Bomb
model considers the NPs that are close to a radiation sensitive cellular target
generate dense secondary electrons and kill the cell according to a probability
distribution, acting like a "bomb".
Methods: TDRA plus a distance model was used as the
theoretical basis for calculating the change in α of the linear-quadratic
survival model and the relative biological effectiveness (RBE). In TDRA,
cellular lesions are assumed to be formed as a result of the combination of
pairs of sublesions (e.g., chromosome break) in the sensitive sites of the
cell. In addition, the yield of sublesions formed within spherical sites is
assumed to be proportional to the energy deposited to the site. We calculated
the quantities for SQ20B and Hela human cancer cells under 250kVp x-ray
irradiation with the presence of gadolinium-based NPs (AGuIXTM), and 220kVp
x-ray irradiation with the presence of 50 nm Gold NPs (AuNPs), respectively,
and compared with existing experimental data. Geant4 based Monte Carlo (MC)
simulations were used to (1) generate the electron spectrum and the phase space
data of photons entering the NPs and to (2) calculate the proximity functions
and other related parameters for the TDRA and the Bomb model.
Results: The Auger cascade electrons have greater proximity
function than photoelectric and Compton electrons in water by up to 30%, but
the resulting increases in α are smaller than those derived from experimental
data. The calculated RBEs cannot explain the experimental findings. The
relative increase in α predicted by TDRA is lower than the experimental result
by a factor of at least 45 for SQ20B cells with AGuIX under 250kVp x-ray
irradiation; and at least 4 for Hela cells with AuNPs under 220kVp x-ray irradiation.
The application of the Bomb model to Hela cells with AuNPs under 220kVp x-ray
irradiation indicated that a single ionization event in NPs caused by higher
energy photons has a greater probability of killing a cell. NPs that are closer
to the cell nucleus are more effective for radiosensitization. The comparison
of Hela cell with AuNPs irradiated with photons of different energy implies
that NP ionization by photon of higher energies have higher killing power, and
the Compton scattering in NP may have a stronger effect than photoelectric
effect, even though the latter can result in Auger cascade.
Conclusion: Microdosimetric calculations of the RBE for cell
death of the Auger electron cascade cannot explain the experimentally observed
radiosensitization by AGuIX or AuNP, while the proposed Bomb model can be a
potential candidate for describing NP-related radiosensitization at low NP
concentrations.
Author(s) Details:
Huagang Yan,
School of Biomedical Engineering, Capital Medical University, Beijing 100069, China.
David J. Carlson,
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wu Liu,
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Please see the link here: https://stm.bookpi.org/ACPR-V4/article/view/13015
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