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GADOLINIUM DOSIMETRY, A PROBLEMATIC GADOLINIUM DOSIMETRY, A PROBLEMATIC ISSUE IN THE NEUTRON CAPTURE THERAPY.ISSUE IN THE NEUTRON CAPTURE THERAPY.COMPARISON BETWEEN EXPERIMENTS AND COMPARISON BETWEEN EXPERIMENTS AND

COMPUTATIONAL SIMULATIONS.COMPUTATIONAL SIMULATIONS.

D.D. BufalinoBufalino, N. Cerullo, V., N. Cerullo, V. ColliColli, , G.G. GambariniGambarini, G., G. RosiRosi

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IntroductionIntroduction

The study on the use of gadolinium as a The study on the use of gadolinium as a neutron absorber in NCT, even if appears neutron absorber in NCT, even if appears quite complex, seems to present some quite complex, seems to present some promising future applications.promising future applications.Therefore this kind of research deserve to Therefore this kind of research deserve to be carried out.be carried out.The aim of this work is to do a first attempt The aim of this work is to do a first attempt of comparison between experimental of comparison between experimental ((FrixyFrixy--gel dosimetergel dosimeter) and computational ) and computational ((MCNPX simulationsMCNPX simulations) results.) results.

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Gadolinium Neutron Capture TherapyGadolinium Neutron Capture Therapy

As predicted byAs predicted by LocherLocher also the use of gadolinium in vice also the use of gadolinium in vice of boron was proposed in NCT in more recent studies.of boron was proposed in NCT in more recent studies.It derived mainly from the consideration of quite higher It derived mainly from the consideration of quite higher neutron capture cross sections of gadolinium (49700 neutron capture cross sections of gadolinium (49700 barns in natural composition) vs. boron (3835 barns for Bbarns in natural composition) vs. boron (3835 barns for B--10) that implies a huge dose delivery in proximity of the 10) that implies a huge dose delivery in proximity of the tumour region.tumour region.Furthermore we can take advantage from the experience Furthermore we can take advantage from the experience gained in use of Gd as contrast agent in MRI.gained in use of Gd as contrast agent in MRI.It has been estimated that a tumour concentration of up to It has been estimated that a tumour concentration of up to 10001000 ppmppm 157157Gd can be achieved with 0.5Gd can be achieved with 0.5 mmolmmol kgkg--11 body body weight of Gdweight of Gd--DTPA DTPA

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GdNCT (Gadolinium neutron capture therapy)GdNCT (Gadolinium neutron capture therapy)

The spectrum of the secondary particles emitted by the The spectrum of the secondary particles emitted by the gadolinium (gadolinium (mainly electronsmainly electrons) is quite complex and, ) is quite complex and, among others, the presence of among others, the presence of strong strong γγ spreads out the spreads out the dose delivery to a broad region, loosing the selectivity of dose delivery to a broad region, loosing the selectivity of the therapy.the therapy.However, Auger electrons are also emitted after the Gd However, Auger electrons are also emitted after the Gd neutron capture and are characterized by a short range, neutron capture and are characterized by a short range, bringing a very high contribute to the local dose delivery bringing a very high contribute to the local dose delivery in GdNCT.in GdNCT.Therefore bothTherefore both microdosimetricmicrodosimetric (tumour dose)(tumour dose) and and macrodosimetricmacrodosimetric (healthy tissue dose)(healthy tissue dose) evaluations are evaluations are necessary.necessary.

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Problematic issues in GdNCTProblematic issues in GdNCTThermal neutron flux undergoes reduction if considerable amount of 157Gd is present and, as a consequence, the therapeutic dose results to be reduced. The total dose and the fraction of therapeutic dose, when a given amount of gadolinium is accumulated, depends on the dimensions of the exposed volume.The γ-dose may be very high. Therefore, it is necessary to make a serious analysis in order to avoid damage to healthy tissue.

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Methods for experimental inMethods for experimental in--phantomphantom dosimetrydosimetry

Gel-dosimetry for imaging all dose components (chemical dosimeter incorporated in a gel matrix)Absorbed dose is imaged and profiledProper gel compositions have been studied in order to separate different dose contributionsThermoluminescence dosimetry (TLD)From differential analysis of the emission of TLDs of different kinds, dose contributions can be separatedActivation technique for inter-comparison of thermal neutron fluence valuesCoupled ionisation chambers for gamma and neutron doses

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FriXyFriXy--gel dosimetergel dosimeterAA FriXyFriXy--gel dosimeter is a FAX (Ferrousgel dosimeter is a FAX (Ferrous--Sulphate/Sulphate/AgaroseAgarose//XylenolXylenol) layered) layered--gel dosimeter gel dosimeter imaged with a portable optical system.imaged with a portable optical system.Conformal radiotherapy can take advantage of this Conformal radiotherapy can take advantage of this dosimeter: in fact it is possible to designdosimeter: in fact it is possible to design FriXyFriXy--gel gel phantoms simulating the situation of interest, with good phantoms simulating the situation of interest, with good tissuetissue--equivalence for all kinds of radiation, except equivalence for all kinds of radiation, except thermal neutrons (in the standard composition).thermal neutrons (in the standard composition).By properly changing gel composition, tissueBy properly changing gel composition, tissue--equivalence for thermal neutrons is obtained.equivalence for thermal neutrons is obtained.The absorbed dose can be 3D imaged with a spatial The absorbed dose can be 3D imaged with a spatial resolution better than 1x0,5x0,5 mmresolution better than 1x0,5x0,5 mm33. .

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Difference in Optical Density between irradiated Difference in Optical Density between irradiated gelgel--samples and reference gel samplesamples and reference gel sample

In ferrous sulphate solutions ionising radiation starts a chain In ferrous sulphate solutions ionising radiation starts a chain of chemical of chemical reactions which results in the conversion of ferrous ions Fereactions which results in the conversion of ferrous ions Fe2+2+ into ferric ions into ferric ions Fe3+.Fe3+.The conversion yield has shown to be proportional, till saturatiThe conversion yield has shown to be proportional, till saturation, to the on, to the absorbed dose. absorbed dose. Therefore, after ionising radiation, from the variation of some Therefore, after ionising radiation, from the variation of some detectable detectable physical parameter depending on the ferrous and ferric ion amounphysical parameter depending on the ferrous and ferric ion amounts, the ts, the absorbed dose can be indirectly determined. absorbed dose can be indirectly determined. In figure the difference in Optical Density between irradiated gIn figure the difference in Optical Density between irradiated gelel--samples samples and reference gel sample, as measured with a spectrophotometer, and reference gel sample, as measured with a spectrophotometer, is is shown. shown.

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InIn--phantomphantom dosimetrydosimetry in NCTin NCT

In-phantom dosimetry measurements have been performed, in a configuration simulating a volume containing a region with accumulation of both 10B (35ppm) and 157Gd (100 ppm) and an amount of both the isotopes lower for a factor 3.5 in the phantom matrix.Phantoms in the form of cylinder, with 16 cm of diameter and 14 cm of height (with a coaxial cylindrical hole of 6 cm if diameter) have been exposed in the epithermal column of 5 kW TAPIRO fast reactor (ENEA, Casaccia) faced to the collimator and with the cylinder axis fitting the beam axis.

1010

InIn--phantomphantom dosimetrydosimetry in NCTin NCTIn-phantom dose profiles versus depth have been drawn utilizing gel-dosimeters in form of layers (3 mm thickness), analyzed with the method set up in the laboratory. All dose contributions have been revealed, that is the doses due to gamma-radiation, fast neutrons, charged particles and electrons.The electron dose has been obtained from the responses of a layer of gel without gadolinium and a layer of gel with gadolinium. The hypothesis has been done that the gamma dose is the same in the two gels, being contiguous layers. If the approximation would not be good, then the electron dose might be even lower than the measured one.In the figures the acquired image of a gel layer In the figures the acquired image of a gel layer irradiated with a Gammairradiated with a Gamma--Knife and the profile, Knife and the profile, generated with the FXY software, are shown.generated with the FXY software, are shown.

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Experimental procedureExperimental procedureThree phantoms have been analysedThree phantoms have been analysed–– Phantom # 1 (Ph1) Phantom # 1 (Ph1) -- Polyethylene shell filled with Polyethylene shell filled with

gel containing 10gel containing 10 ppmppm of of 1010B and 28,6B and 28,6 ppmppm of of 157157GdGd

–– Phantom # 2 (Ph2) Phantom # 2 (Ph2) -- Like Ph1 but with inserted a Like Ph1 but with inserted a cylindrical volume (3 cm high, 7 cm in diameter) cylindrical volume (3 cm high, 7 cm in diameter) containing 35containing 35 ppmppm of of 1010B and 100B and 100 ppmppm of of 157157Gd in Gd in order to simulate a tumourorder to simulate a tumour

–– Phantom # 4 (Ph4) Phantom # 4 (Ph4) -- Polyethylene shell filled with Polyethylene shell filled with gel containing only 10gel containing only 10 ppmppm of of 1010BB

These phantoms was irradiated in the TAPIRO fast These phantoms was irradiated in the TAPIRO fast reactor at the ENEA Casaccia Centre.reactor at the ENEA Casaccia Centre.

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Casaccia Casaccia –– TAPIRO Fast Research ReactorTAPIRO Fast Research Reactor

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Fast reactor TAPIROFast reactor TAPIRO

It is a highly enriched (It is a highly enriched (235235U) U) fast neutron reactorfast neutron reactorNominal power: 5 kW Nominal power: 5 kW (thermal)(thermal)Neutron flux (at coreNeutron flux (at core centercenter): ): 44××10101212 cmcm--22ss--11

Thermal or epithermal Thermal or epithermal facilities can be introduced in facilities can be introduced in the main column.

(b)

(a)the main column.

Vertical (a) and horizontal (b) sections of TAPIRO

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Thermal neutron fluxThermal neutron flux profiles obtained for profiles obtained for the three different phantom types.the three different phantom types.

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Gamma doseGamma dose profiles vs. depth in the three profiles vs. depth in the three studied phantomsstudied phantoms

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Dose rate in the central axis of phantom # 2Dose rate in the central axis of phantom # 2 containing 10containing 10ppmppm of of 1010B and 28.6B and 28.6 ppmppm of of 157157Gd and with simulation of aGd and with simulation of a

tumortumor with 35with 35 ppmppm of of 1010B and 100B and 100 ppmppm of of 157157GdGd

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The same dose profiles in RBE The same dose profiles in RBE valuesvalues

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Significant considerationsSignificant considerationsThe total electron dose has resulted to be a very low percentage of the total dose in the examined configuration. Here, the region with accumulation of 157Gd is a cylinder with 7 cm of diameter and 3 cm of height.If the same concentration of gadolinium is accumulated in smaller volumes, then the total gamma dose is lower and the relative electron dose higher. In this work, the amount of 157Gd has been chosen with the intention of performing also nuclear magnetic resonance imaging (NMRI), sincegadolinium is already utilized as image intensifier in NMRI.An interesting feature is the fact that if B and Gd are joined iAn interesting feature is the fact that if B and Gd are joined in the same n the same molecule, the neutron flux reduction (due to Gd) is measurable, molecule, the neutron flux reduction (due to Gd) is measurable, and we and we can take advantage of this feature to measure the can take advantage of this feature to measure the ““carriercarrier”” moleculemoleculeconcentrationandconcentrationand consequently B concentration (neutron radiography).consequently B concentration (neutron radiography).

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Calculation vs. experiment Calculation vs. experiment comparisoncomparison

At Pisa University, in the last years some analysis were At Pisa University, in the last years some analysis were carrcarriedied out by NCT group both in BNCT and in GdNCTout by NCT group both in BNCT and in GdNCTdosimetrydosimetry. At the present these researches are . At the present these researches are continued on both these issues, mainly on the continued on both these issues, mainly on the macrodosimetric aspect, also undertaking a PhD thesis macrodosimetric aspect, also undertaking a PhD thesis on this topic. In this frame some simulations, using MC on this topic. In this frame some simulations, using MC code, were performed in order to evaluate the dose code, were performed in order to evaluate the dose distribution due to Gd reactions. distribution due to Gd reactions. At the Boston congress the results of physical At the Boston congress the results of physical measurements performed by researchers of Milan measurements performed by researchers of Milan University at the TAPIRO reactor (ENEA, Casaccia) on University at the TAPIRO reactor (ENEA, Casaccia) on phantoms containing B and Gd were presented.phantoms containing B and Gd were presented.A comparisons between simulation and experimental A comparisons between simulation and experimental results have been done. results have been done.

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MCNP Tapiro schemeMCNP Tapiro scheme(used in MCNPX simulation)(used in MCNPX simulation)

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Neutron spectrum calculated with Neutron spectrum calculated with MCNPX at the outer part of epithermal MCNPX at the outer part of epithermal

columncolumn

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Thermal neutron flux (< 1Thermal neutron flux (< 1 eVeV) ) behaviourbehaviour

Note: the noticeable thermal flux depression in presence of gadoNote: the noticeable thermal flux depression in presence of gadolinium linium is confirmed.is confirmed.

Experimental MCNPX evaluation

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Gamma dose behaviourGamma dose behaviour(from n,(from n,γγ reaction)reaction)

Note: In MCNPX we have taken into account also photonuclear Note: In MCNPX we have taken into account also photonuclear reactions using models present in the code when tabular data arereactions using models present in the code when tabular data are not not

available. Larger gamma flux in Gd containing phantoms is confiavailable. Larger gamma flux in Gd containing phantoms is confirmed.rmed.Experimental MCNPX evaluation

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ConclusionsConclusions

The task of this work was to compare The task of this work was to compare experiments with computational simulation of experiments with computational simulation of materials containing gadolinium.materials containing gadolinium.In fact published experimental data are poor or In fact published experimental data are poor or nonnon--existent and so the experiments done by existent and so the experiments done by University of Milan are University of Milan are very important.very important.Also the computational simulations performed at Also the computational simulations performed at the University of Pisa have been quite the University of Pisa have been quite interesting.interesting.The preliminary comparisons gave good results The preliminary comparisons gave good results and the work deserve to be continued.and the work deserve to be continued.