Page 293 - 2014 Printable Abstract Book
P. 293
probability of creating DSB, SSB, clustered damage and multiple-hits in the same target. The probabilities
for these damage patterns have values of 2.5%, 4.3%, 6.7% and 5.4%, respectively. Isolated damage is
most probable between 700 eV to 900 eV with a probability of 0.2%. In conclusion, we obtained DNA
damage probability distributions as a function of electron incident energy. We showed that electrons with
kinetic energies between 50 and 250 eV have the highest probability of producing complex forms of DNA
damage (DSB, SSB+). We also showed that double ionisations within the same DNA target is the most
frequent outcome occurring 5% of the time. It is expected that electron slowing down spectra can be
convolved with our formalism to calculate source specific DNA damage patterns.
(PS5-12) Comparison of the efficacy of gold nano-particle induced radiosensitization for proton and
photon therapy. Jan P.O. Schuemann, PhD; Yuting Lin, PhD; and Harald Paganetti, PhD
Massachusetts General Hospital, Boston, MA
Motivation: The potential to use gold nanoparticles (GNPs) as radiosensitizer for photon radiation
therapy has been widely investigated, however, only a few studies have been published for GNP induced
radiosensitization for proton irradiation. Approach: We compare the effects of the presence of GNPs for
three treatment modalities: a clinical proton field, 6 MV photons and two kV photon fields. For each
modality we first investigated nanodosimetric dose distributions. Then, we used a a generic cell model to
quantify the radiosensitization potential for GNPs internalized in tumor cells. We placed GNPs outside the
cell, inside the cytoplasm, inside the lysosome and randomly distributed inside the cell including the
nucleus. We calculated the biological effect using a model that predicts dose-response curves using
particle track structures (local effect model). Finally, we investigated vasculature damage induced by 20
mg/g GNPs in blood for the three modalities for vessel diameters of 8-20 μm. All our studies are based on
Monte Carlo simulations using TOPAS (Tool for Particle Simulations). Results: We find that the mechanism
by which GNPs cause dose enhancements differs between photons and protons. The GNP dose
enhancement factor for protons is energy independent and as high as 15. For photons the factor is highly
energy dependent. Secondary electrons produced by kV photon have the longest range in water. At 10
μm from the GNP surface kV photons cause a 20 times larger dose enhancement than protons. We find
that, due to the shorter range of secondary electrons, the GNP sensitization for protons is highly sensitive
to where in the cell GNPs are localized. For the same GNP uptake and concentration, kilovoltage photons
cause most cell damage, for GNPs in the cytoplasm (randomly distributed) the maximum enhancement
ratios were found to be 1.3, 1.1 and 1.03 (1.5, 1.4 and 1.01) for kV photons, protons and MV photons,
respectively. For the vasculature we found the additional dose to the inner vessel wall to be 130%, 115%
and 102% of the prescribed dose for kV photons, protons and MV photons, respectively. Conclusion: kV
photons show the largest enhancement of biological effects, especially if GNPs do not get internalized by
cells. If GNPs are partially internalized in the nucleus protons can cause damage enhancement comparable
to kV photons.
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for these damage patterns have values of 2.5%, 4.3%, 6.7% and 5.4%, respectively. Isolated damage is
most probable between 700 eV to 900 eV with a probability of 0.2%. In conclusion, we obtained DNA
damage probability distributions as a function of electron incident energy. We showed that electrons with
kinetic energies between 50 and 250 eV have the highest probability of producing complex forms of DNA
damage (DSB, SSB+). We also showed that double ionisations within the same DNA target is the most
frequent outcome occurring 5% of the time. It is expected that electron slowing down spectra can be
convolved with our formalism to calculate source specific DNA damage patterns.
(PS5-12) Comparison of the efficacy of gold nano-particle induced radiosensitization for proton and
photon therapy. Jan P.O. Schuemann, PhD; Yuting Lin, PhD; and Harald Paganetti, PhD
Massachusetts General Hospital, Boston, MA
Motivation: The potential to use gold nanoparticles (GNPs) as radiosensitizer for photon radiation
therapy has been widely investigated, however, only a few studies have been published for GNP induced
radiosensitization for proton irradiation. Approach: We compare the effects of the presence of GNPs for
three treatment modalities: a clinical proton field, 6 MV photons and two kV photon fields. For each
modality we first investigated nanodosimetric dose distributions. Then, we used a a generic cell model to
quantify the radiosensitization potential for GNPs internalized in tumor cells. We placed GNPs outside the
cell, inside the cytoplasm, inside the lysosome and randomly distributed inside the cell including the
nucleus. We calculated the biological effect using a model that predicts dose-response curves using
particle track structures (local effect model). Finally, we investigated vasculature damage induced by 20
mg/g GNPs in blood for the three modalities for vessel diameters of 8-20 μm. All our studies are based on
Monte Carlo simulations using TOPAS (Tool for Particle Simulations). Results: We find that the mechanism
by which GNPs cause dose enhancements differs between photons and protons. The GNP dose
enhancement factor for protons is energy independent and as high as 15. For photons the factor is highly
energy dependent. Secondary electrons produced by kV photon have the longest range in water. At 10
μm from the GNP surface kV photons cause a 20 times larger dose enhancement than protons. We find
that, due to the shorter range of secondary electrons, the GNP sensitization for protons is highly sensitive
to where in the cell GNPs are localized. For the same GNP uptake and concentration, kilovoltage photons
cause most cell damage, for GNPs in the cytoplasm (randomly distributed) the maximum enhancement
ratios were found to be 1.3, 1.1 and 1.03 (1.5, 1.4 and 1.01) for kV photons, protons and MV photons,
respectively. For the vasculature we found the additional dose to the inner vessel wall to be 130%, 115%
and 102% of the prescribed dose for kV photons, protons and MV photons, respectively. Conclusion: kV
photons show the largest enhancement of biological effects, especially if GNPs do not get internalized by
cells. If GNPs are partially internalized in the nucleus protons can cause damage enhancement comparable
to kV photons.
291 | P a g e
