Ahmad, R

Fracchiolla, F

Lourenco, A

Ricketts, K

Royle, G

Schwarz, M

UCL Discovery

Novel method to quantify physical dose enhancement due to gold nanoparticles in proton therapyR. Ahmad1, 2, G. Royle2, A.M. Lourenco2, 3, M Schwarz4, 5, F Fracchiolla4, K. Ricketts1 1 Division of Surgery and Interventional Science, University College London, London, NW3 2QG2 Department of Medical Physics and Bioengineering, University College London, London, WC1E 6BT3 Acoustics and Ionizing Radiation Team, National Physical Laboratory, Teddington, United Kingdom4 Protontherapy Department, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy5 Trento Institute for Fundamental Physics and Applications (TIFPA), National Institute of Nuclear Physics (INFN), Trento, ItalyContact: reem.ahmad.11@ucl.ac.ukIntroductionGold nanoparticles (GNPs) increase dose deposition when localisedto the tumourStudies have demonstrated this in cell and animal studies throughan increase in survival rates 1,2Monte Carlo studies have modelled physical dose enhancement 3Many biological studies have been performed demonstrating doseenhancement, however these do not quantify physical doseenhancementThe present study demonstrates a novel method to quantifyphysical dose enhancement using Gafchromic films and a custommade phantomAimTo quantify the physical dose enhancement of GNPs throughGafchromic film measurementsMethodThe phantom (figure 1) contained slits at 1 mm intervals to hold filmsheets at various depthsPhantom was comprised of PMMA as this is commonly used inproton therapy for its water equivalenceThe phantom was positioned within the width of the Bragg peak toallow for a high resolution depth dose plotEBT3 Gafchromic films (Ashland, USA) were used for themeasurementsSolid water slabs (Gammex, Middleton, WI) were used to createsufficient build up (29.1 cm) in front of the phantom to tune Braggpeak position to within the phantom (figure 2)Measurements were carried out at the Trento proton therapy centreusing a 226 MeV proton beamMeasurements were taken for both water and water + GNP solutionConcentrations of GNPs used were 5.5 and 1.1 mgAu/mlEach depth was irradiated with 20 MU corresponding to a doserange of 6-37 cGyFilms were calibrated covering a dose range from 0-250 cGy, using aclinically used procedureFilms were scanned after 24 hours using an EPSON desktop scannerDepth dose plots were used to determine the level of doseenhancementDose enhancement is defined as the ratio of the dose with andwithout GNPs for the depth being consideredFigure 1: Custom made filmphantom containing GNPs and aGafchromic film. Phantom allowsfor measurements to be taken at1 mm intervalsResultsConsidering the depth dose plot (figure 3) it can be seen that there isan increase in dose deposition with the introduction of GNPsDose deposition increases by 26%±0.53 with 1.1 mg/ml and21%±0.53 with 5.5 mg/mlIt was expected that dose enhancement would increase withconcentration, whereas these results showed a higher enhancementwith the lower concentrationOther studies have shown Gafchromic films to be prone to quenchingeffects which could have had a greater effect at higher concentrations,leading to the lower enhancement observed 4 As well as dose enhancement a 2.2 mm longitudinal shift of the distaledge was shown with 5.5 mg/ml of GNPs Shape changes must be taken into account to ensure the entiretumour is irradiated and there are no under dosed regionsConclusions GNP concentration of 1.1 mg/ml showed a higher dose enhancementof 26% compared to 21% for 1.1 mg/ml Longitudinal shift was shown only with 5.5 mg/ml and was found tobe 2.2 mm Effects of GNP concentrations were shown through measurement ofphysical dose enhancement Reasons for not having an increase in dose deposition with increasingconcentration could be due to quenching effects Changes to the Bragg peak shape due to the presence of GNPs needsto be accounted for in future studies to ensure full tumour coverage These results demonstrate physical dose enhancement alone Cellular studies should be performed to determine how physical doseenhancement by GNPs translates to biological systemsFuture work Investigate the effects of GNP enhancement on treatment plans,assessing any changes that need to be made Parallel cell studies to determine biological effect resulting fromphysical dose enhancementReferences1. Liu et al. Enhancement of cell radiation sensitivity by pegylated gold nanoparticles, Physics in medicine and biology, 55.4 (2010) 9312. Kim et al. Enhanced proton treatment in mouse tumors through proton irradiated nanoradiator effects on metallic nanoparticles, Physics in medicine and biology, 57.24 (2012) 83093. Wälzlein et al. Simulations of dose enhancement for heavy atom nanoparticles irradiated by protons, Physics in medicine and biology, 59.6 (2014) 14414. Kirby et al. LET dependence of GafChromic films and an ion chamber in low-energy proton dosimetry, Physics in medicine and biology, 55.2 (2009) 417Figure 2:Experimental setupwith solid waterequivalent to 29.1cm of water followedby the film phantomwith innerdimensions of 4.1cm. Phantom wasfilled with eitherwater or a water +GNP solution of aknown concentrationFigure 3: Depth doseplot normalized topeak water dose toshow the level ofenhancement withGNP concentrations of1.1 and 5.5 mg/ml.Errors correspond totwo standarddeviations.Figure 4: Depth doseplot normalized topeak dose of thematerial to show thechanges caused to theshape of the Braggpeak with GNPconcentrations of 1.1and 5.5 mg/ml. Errorscorrespond to twostandard deviations.

Novel method to quantify physical dose enhancement due to gold nanoparticles in proton therapy

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Novel method to quantify physical dose enhancement due to gold nanoparticles in proton therapy

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