E‑mail: sdsbarc@ gmail.com Dose enhancement in gold nanoparticle‑aided radiotherapy for the therapeutic photon beams using Monte Carlo technique ABSTRACT Background: Gold nanoparticle
Trang 1Nitin Ramesh Kakade, Sunil Dutt Sharma
Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Anushakti Nagar, Mumbai, Maharashtra, India
For correspondence:
Dr Sunil Dutt Sharma, Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, CTCRS, Building, Anushakti Nagar, Mumbai ‑ 400 094, Maharashtra, India E‑mail: sdsbarc@ gmail.com
Dose enhancement in gold nanoparticle‑aided
radiotherapy for the therapeutic photon
beams using Monte Carlo technique
ABSTRACT
Background: Gold nanoparticle (GNP)‑aided radiation therapy (RT) is useful to make the tumor more sensitive to radiation damage
because of the enhancement in the dose inside the tumor region Polymer gel dosimeter (PGD) can be a good choice for the physical
measurement of dose enhancement produced by GNP inside the gel.
Materials and Methods: The present study uses EGSnrc Monte Carlo code to estimate dose enhancement factor (DEF) due to the
introduction of GNPs inside the PGD at different concentrations (7 and 18 mg Au/g of gel) when irradiated by therapeutic X‑rays of
energy 100 kVp, 150 kVp, 6 MV, and 15 MV The simulation was also carried out to quantify the dose enhancement in PAGAT gel
and tumor for 100 kVp X‑rays.
Results: For 100 kVp X‑rays, average DEF of 1.86 and 2.91 is observed in the PAGAT gel dosimeter with 7 and 18 mg Au/g of
gel, respectively Average DEF of 1.69 and 2.61 is recorded for 150 kVp X‑rays with 7 and 18 mg Au/g of gel, respectively No
clinically meaningful DEF was observed for 6 and 15 MV photon beams Furthermore, the dose enhancement within the PAGAT gel
dosimeter and tumor closely matches with each other.
Conclusion: The polymer gel dosimetry can be a suitable method of dose estimation and verification for clinical implementation
of GNP‑aided RT GNP‑aided RT has the potential of delivering high localized tumoricidal dose with significant sparing of normal
structures when the treatment is delivered with low energy X‑rays.
KEY WORDS: Dose enhancement factor, gel dosimeter, gold nanoparticle, Monte Carlo, radiation therapy
Original Article
INTRODUCTION
External beam radiotherapy (RT) is currently one
of the most common and effective treatment
modalities used for the treatment of cancer The
objective of RT is to deliver an adequate dose to the
tumor while sparing surrounding normal tissue
The accurate dose measurement with the help of
suitable dosimetry tools is the main requirement
for success of RT Historically, orthovoltage X‑rays
were used for treating superficial lesions However,
with the availability of state of the art medical
electron linear accelerator deep‑seated tumor could
well be managed by highly penetrating X‑rays
Following the work by Hainfeld et al.,[1] there
has been considerable interest in the use of gold
and other heavy‑atom containing nanoparticles
to enhance the dose delivered to tumors Gold
nanoparticle (GNP)‑aided RT is useful to make
the tumor more sensitive to radiation damage
because of the enhancement in the dose inside
the tumor region The enhancement in the tumor
region primarily occurs due to enhancement
in photoelectric cross section because of the introduction of GNPs (Z = 79) into the tumor volume.[2]
The dosimetric suitability of GNP‑aided RT is very crucial to justify its feasibility and applicability in clinical practice Polymer gel dosimeter (PGD) with tissue like elemental composition have the unique advantage of providing three‑dimensional dose information with high spatial resolution.[3] PGD used to quantify absorbed dose via measuring the polymerization of the monomer by radiation PGD can be read out with a magnetic resonance imaging scanner[4] or optical computed tomography scanner.[5]
The effects of contrast agents can be easily quantified using polymer gels.[6] They are very good choice for the physical measurement of the dose enhancement produced by high Z GNP inside the gel dosimeter
Hainfeld et al reported in vivo study of using
gold as a radiosensitive agent Irradiation using 250 kVp X‑rays resulted in 66% increase
in 1‑year survival rates of cancer‑bearing mice
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.147691 PMID: ***
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Trang 2Kakade and Sharma: MC calculated DEF in gel dosimeter and tumor
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Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
when compared to irradiation without the implanted gold
Cho et al.[7] quantified dose enhancement factor (DEF) with
the infusion of GNPs with various concentrations using
photon‑emitting brachytherapy sources Khadem‑Abolfazli
et al.[6] investigated dose enhancement due to GNP in MAGICA
polymer gel both experimentally and by simulation for 18 MV
X‑rays Zhang et al.[8] studied the dose enhancement with an
uniform distribution of 100 nm diameter GNPs irradiated by
192Ir brachytherapy source using the GEANT4 Monte Carlo (MC)
code
To our knowledge, limited information is available on the
use of PGD for possible dose enhancement due to the use of
GNPs The goal of the present study was to use EGSnrc MC[9]
code for estimating DEF due to the introduction of GNPs in
the PGD at concentration levels of 7 and 18 mg Au/g of gel
respectively The DEF within the PAGAT gel dosimeter was
estimated when it is irradiated by therapeutic X‑rays of energy
100 kVp, 150 kVp, 6 MV, and 15 MV Also to see the dosimetric
suitability of PAGAT gel dosimeter, the dose enhancement in
PAGAT gel and tumor is quantified for 100 kVp X‑rays at the
above mentioned concentration levels
MATERIALS AND METHODS
EGSnrc Monte Carlo code system
The EGSnrc MC code system is a general purpose package for
the MC simulation for the coupled transport of electrons and
photons in arbitrary geometry for particles with energies
above a few kiloelectronvolt up to several hundreds of
gigaelectronvolt EGSnrc uses material cross section created
by the companion code PEGS4 The electron cut‑off energy
and photon cut‑off energy of 0.521 MeV and 0.01 MeV
respectively were chosen, during the use of PEGS4 and
EGSnrc codes The low energy threshold for the production
of knock‑on electrons (AE) is set to 0.521 MeV, and the
threshold for the secondary Bremsstrahlung photon (AP)
were set to 10 keV
Geometry and dose enhancement factor estimation
PAGAT is a normoxic polyacrylamide and gelatine type gel
that uses tetrakis (hydroxymethyl) phosphonium chloride to
scavenge contaminating oxygen‑free radicals The chemical
and elemental compositions of PAGAT gel were taken from the
literature.[10] The material composition of the tumor and normal
tissue was assumed to be the same having 10.1% hydrogen,
11.1% carbon, 2.6% nitrogen, and 76.2% oxygen defined
by the International Commission on Radiation Units and
Measurements (ICRU).[11] The composition and density of the
PAGAT gel were altered by varying the concentration levels of
GNPs (7 and 18 mg Au/g gel) inside the gel medium as indicated
in the study by Hainfeld et al Furthermore, the composition
and density of the tumor were altered by varying the
concentration levels of GNPs (7 and 18 mg Au/g tumor) inside
the tumor In each of the simulation case, it was considered
that the GNPs were uniformly distributed throughout the gel and tumor
For the MC simulation, a cylindrical water phantom of radius
15 cm and height 30 cm was used The PGD was taken as a cylinder of 0.5 cm radius and 5 cm height Figure 1 presents the setup geometry used in MC simulation A field size of 5 × 5 cm2 was defined at a source‑to‑surface distance of 20 and 100 cm for kilovoltage and megavoltage X‑rays, respectively The DEFs (the ratio of dose with and without GNP) were computed
by placing the gel dosimeter at a depth of 1 cm and 5 cm from the phantom surface, respectively, for kilovoltage and megavoltage X‑rays In the second case, the gel dosimeter was replaced by the tumor and the surrounding water was replaced
by the ICRU four component tissues The MC simulation was repeated for 100 kVp X‑rays to verify the dosimetric suitability
of polymer gel dosimetry
RESULTS
Variation of dose enhancement factor with gold nanoparticle concentration
The average DEF within the gel dosimeter with different concentrations of GNPs for the therapeutic X‑rays are summarized in Table 1 For 100 kVp X‑rays, average DEF of 1.86 and 2.91 is observed in the gel dosimeter with 7 and
18 mg GNP concentration, respectively On the other hand, average DEF of 1.69 and 2.61 is recorded for 150 kVp X‑rays
Figure 1: Schematic diagram showing the geometry used in the Monte
Carlo simulation
Table 1: Average DEF for two different concentrations of GNP in gel dosimeter for kilovoltage and megavoltage therapeutic X‑rays
Concentration
DEF=Dose enhancement factor, GNP=Gold nanoparticle
Trang 3with 7 and 18 mg GNP concentration, respectively It is also
observed from the data in this table that the DEF increases
with the increasing GNP concentration in the gel dosimeter for
kilovoltage X‑rays However, no observable dose enhancement
is observed for 6 and 15 MV photon beams either for average
DEF or DEF at different depths [Figures 2 and 3]
Variation of dose enhancement factor with depth in the gel
dosimeter
Figure 4 shows the comparison of DEF for 7 and 18 mg GNP
concentration at 100 and 150 kVp X‑rays, respectively It is
observed from this figure that the dose enhancement occurs in
the gel dosimeter loaded with GNP while dose reduction takes
place in the water region beyond the gel region infused with
GNPs The dose reduction in the water region is proportional
to the photon energy and the GNPs concentration in gel
dosimeter
Over the gel dosimeter region for 100 kVp X‑rays, the DEF
decreases by 8.75 and 21% for 7 and 18 mg GNP concentration,
respectively On the other hand, for 150 kVp X‑rays, the DEF decreases moderately by 1 and 11% for 7 and 18 mg GNP concentration, respectively This indicates that the fall‑off of DEF over the gel volume is more for 100 kVp X‑rays
Dose enhancement factor in PAGAT gel and tumor for
100 kVp X‑ray
The DEF within the PAGAT gel dosimeter and tumor are quantified for 100 kVp X‑rays at different GNP concentration levels, and results are presented in Table 2 The percentage variation of 0.54 and 1% is observed in the DEF for GNP concentration of 7 and 18 mg Figures 5 and 6 show the variation of DEF within gel dosimeter and tumor at GNP concentration of 7 and 18 mg, respectively In this figure, the factors shown beyond 6 cm are not the DEFs but show a decrease in the doses behind the gel and tumor loaded with
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Figure 2: Variation of dose enhancement factor with depth for 6 MV
X‑rays at two different gold nanoparticle concentrations
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Figure 3: Variation of dose enhancement factor with depth for 15 MV
X‑rays at two different gold nanoparticle concentrations
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Figure 4: A comparison of dose enhancement factor for 100 and 150
kVp X‑rays at different gold nanoparticle concentrations
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Figure 5: A comparison of dose enhancement factor for polymer gel
and tumor at 7 mg gold nanoparticle concentration for 100 kVp X‑rays
Table 2: A comparison of average DEF for two different GNP concentrations in gel dosimeter and tumor at 100 kVp X‑ray
DEF=Dose enhancement factor, GNP=Gold nanoparticle
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Journal of Cancer Research and Therapeutics - January-March 2015 - Volume 11 - Issue 1
GNPs This result indicates that the dose enhancement within
gel dosimeter and tumor closely matches with each other
DISCUSSION
Average DEF in the gel dosimeter region with the infusion
of GNPs was estimated by MC simulations for therapeutic
kilovoltage and megavoltage photon beams The results show
that 100 and 150 kVp X‑rays provides dose enhancement by a
factor of 2–3 for GNP concentration considered in this study
On the other hand, it would be difficult to achieve such a dose
enhancement with high energy photon beams because of the
predominance of Compton effect Furthermore, it is observed that
dose enhancement in the gel dosimeter and tumor region are in
good agreement with each other This shows that the polymer
gel dosimetry can be very good method of dose estimation and
verification for clinical implementation of GNP aided RT
The aim of the current study was to provide impetus for further
investigation, and clinical implementation of GNP‑aided RT for
many types of tumor that can be treated with external beam
therapy The tumor dose enhancement for this treatment situation
would be significant especially when the delivery of a tumor dose
becomes difficult due to the limitation of normal tissue tolerance
dose Experimental work to validate such a dose enhancement
by GNPs using PGD is currently under investigation
CONCLUSION
The MC simulation was carried out to estimate the dose
enhancement in the PGD containing different concentration
of GNPs when irradiated with various X‑ray beams commonly
used in clinical practice The PGD, PAGAT gel with tissue
like elemental composition can be used for the dosimetric
feasibility of the GNP‑aided RT This study indicates that GNP
aided RT has the potential of delivering very high localized tumoricidal dose with significant sparing of normal structures and organs at risk when the treatment is delivered with low energy X‑rays after an introduction of GNPs into the tumor
ACKNOWLEDGMENTS
The authors are grateful to Dr D N Sharma, Director, Health, Safety and Environment Group, Bhabha Atomic Research Centre (BARC) and Shri D A R Babu, Head, Radiological Physics and Advisory Division (RPAD), BARC for their constant encouragement.
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of gold nanoparticle‑aided radiation therapy (GNRT) via brachytherapy using low‑energy gamma‑/x‑ray sources Phys Med Biol 2009;54:4889‑905.
8 Zhang SX, Gao J, Buchholz TA, Wang Z, Salehpour MR, Drezek RA,
et al Quantifying tumor‑selective radiation dose enhancements
using gold nanoparticles: A Monte Carlo simulation study Biomed Microdevices 2009;11:925‑33.
9 Kawrakow I, Rogers DW The EGSnrc Code System, Monte Carlo Simulation of Electron and Photon Transport Ottawa, Canada: Technical Report No PIRS –701, National Research Council of Canada; 2006.
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11 International Commission on Radiation Units and Measurements (ICRU) Tissue Substitutes in Radiation Units and Measurement, ICRU Report No 44, Bethesda, USA; 1989.
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Figure 6: A comparison of dose enhancement factor for polymer gel
and tumor at 18 mg gold nanoparticle concentration for 100 kVp X‑rays
Cite this article as: Kakade NR, Sharma SD Dose enhancement in gold
nanoparticle-aided radiotherapy for the therapeutic photon beams using Monte Carlo technique J Can Res Ther 2015;11:94-7.
Source of Support: Nil, Conflict of Interest: None declared.
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... Kakade NR, Sharma SD Dose enhancement in goldnanoparticle- aided radiotherapy for the therapeutic photon beams using Monte Carlo technique J Can Res Ther 2015;11:94-7.... estimate the dose
enhancement in the PGD containing different concentration
of GNPs when irradiated with various X‑ray beams commonly
used in clinical practice The PGD, PAGAT...
verification for clinical implementation of GNP aided RT
The aim of the current study was to provide impetus for further
investigation, and clinical implementation of GNP? ?aided RT for
many