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2015 ; 42
(10
): 5890-902
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Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons,
megavoltage photons, and kilovoltage photons
#MMPMID26429263
Lin Y
; Paganetti H
; McMahon SJ
; Schuemann J
Med Phys
2015[Oct]; 42
(10
): 5890-902
PMID26429263
show ga
PURPOSE: The purpose of this work is to investigate the radiosensitizing effect
of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage
(MV) photon, and kilovoltage (kV) photon irradiation. METHODS: Monte Carlo
simulations were carried out using tool for particle simulation (TOPAS) to obtain
the spatial dose distribution in close proximity up to 20 ?m from the GNPs. The
spatial dose distribution from GNPs was used as an input to calculate the dose
deposited to the blood vessels. GNP induced vasculature damage was evaluated for
three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV
photon beam, and two kV photon beams). For each particle source, various depths
in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14,
and 20 ?m) were investigated. Two GNP distributions in lumen were considered,
either homogeneously distributed in the vessel or attached to the inner wall of
the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo
enhancement studies and conventional clinical fractionation, respectively.
RESULTS: These simulations showed that for 20 Au-mg/g GNP blood concentration
homogeneously distributed in the vessel, the additional dose at the inner
vascular wall encircling the lumen was 43% of the prescribed dose at the depth of
treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1%
for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular
wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more
dose in the vascular wall at 20 cm depth in water as compared to at depth of
maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the
vascular wall for all depths across the spread out Bragg peak with 12.7 cm range
and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter
GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When
the GNPs were attached to the inner vascular wall, the damage to the inner
vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon
source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though
the average dose increase from the proton beam and MV photon beam was not large,
there were high dose spikes that elevate the local dose of the parts of the blood
vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the
GNPs can be actively targeted to the endothelial cells. CONCLUSIONS: GNPs can
potentially be used to enhance radiation therapy by causing vasculature damage
through high dose spikes caused by the addition of GNPs especially for
hypofractionated treatment. If GNPs are designed to actively accumulate at the
tumor vasculature walls, vasculature damage can be increased significantly. The
largest enhancement is seen using kilovoltage photons due to the photoelectric
effect. Although no significant average dose enhancement was observed for the
whole vasculature structure for both MV photons and protons, they can cause high
local dose escalation (>15 Gy) to areas of the blood vessel that can potentially
contribute to the disruption of the functionality of the blood vessels in the
tumor.