AUTHOR QUERIES - TO BE ANSWERED BY THE CORRESPONDING AUTHOR

Journal: Article id: Article title: First Author: Corr. Author: RADIATION PROTECTION DOSIMETRY ncm181 DOSE DISTRIBUTIONS IN PHANTOMS IRRADIATED IN THERMAL COLUMNS OF TWO DIFFERENT NUCLEAR REACTORS G. Gambarini G. Gambarini AUTHOR QUERIES - TO BE ANSWERED BY THE CORRESPONDING AUTHOR The following queries have arisen during the typesetting of your manuscript. Please answer these queries by marking the required corrections at the appropriate point in the text. AQ1 The term b in the following equations 10 B(n,α) 7 Li (σ = 3837 b) and 1 H(n,γ) 2 H (σ = 0.33 b) has not been referred to any constant or variable in the text. Please provide the required expansion for the term. AQ2 Please update reference 2 with the required publication details.

Radiation Protection Dosimetry (2007), pp. 1 5 doi:10.1093/rpd/ncm181 5 10 15 DOSE DISTRIBUTIONS IN PHANTOMS IRRADIATED IN THERMAL COLUMNS OF TWO DIFFERENT NUCLEAR REACTORS G. Gambarini 1,*, S. Agosteo 2, S Altieri 3, S. Bortolussi 3, M. Carrara 4,S.Gay 1,E.Nava 5, C. Petrovich 4, G. Rosi 6 and M. Valente 1 1 Department of Physics of University and INFN Sezione di Milano, Milan, Italy 2 Department of Nuclear Engineering of Polytechnic and INFN Sezione di Milano, Milan, Italy 3 Department of Nuclear and Theoretical Physics of University and INFN Sezione di Pavia, Pavia, Italy 4 Medical Physics Department, National Cancer Institute, Milan, Italy 5 ENEA FIS NUC, Bologna, Italy 6 ENEA FIS ION, S. Maria di Galeria, Roma, Italy 60 65 70 20 In-phantom dosimetry studies have been carried out at the thermal columns of a thermal- and a fast-nuclear reactor for investigating: (a) the spatial distribution of the gamma dose and the thermal neutron fluence and (b) the accuracy at which the boron concentration should be estimated in an explanted organ of a boron neutron capture therapy patient. The phantom was a cylinder (11 cm in diameter and 12 cm in height) of tissue-equivalent gel. Dose images were acquired with gel dosemeters across the axial section of the phantom. The thermal neutron fluence rate was measured with activation foils in a few positions of this phantom. Dose and fluence rate profiles were also calculated with Monte Carlo simulations. The trend of these profiles do not show significant differences for the thermal columns considered in this work. 75 80 25 30 35 INTRODUCTION The interest in boron neutron capture therapy (BNCT) of explanted organs is growing worldwide for the promising results of the first treatment of an explanted liver in the thermal column of TRIGA MARK II reactor of the University of Pavia (1). BNCT takes advantage of the possibility of accumulating selectively the 10 B isotope in tumour cells together with the high cross-section of the thermal neutron reaction 10 Bðn; aþ 7 Li ðs ¼ 3837bÞ: Q1 40 Owing to the high linear energy transfer (LET) and relative biological effectiveness (RBE) of a and 7 Li particles, BNCT is potentially effective for radioresistant tumours. Moreover, the energy release of the reaction products is localised within the tumour 45 cells because of their short range in tissue (,10 mm). Therefore, BNCT is of particular interest for the treatment of diffused tumours, such as liver metastases. An uniform spatial distribution of the absorbed 50 dose in the whole volume of the treated organ is a fundamental requirement for undertaking the study and the planning of this therapy. Reliable evaluations of both the therapeutic dose and the dose in the healthy tissue are necessary, and for this purpose 55 the dose contributions of the secondary radiation components having different biological effect should * Corresponding author: grazia.gambarini@mi.infn.it be determined separately. In particular, the gamma dose and the dose due to the charged particles (a and 7 Li) generated by thermal neutrons on 10 Bhave to be measured. The gamma dose is due to the reactor background and to the thermal neutron capture on hydrogen 1 Hðn; gþ 2 H ðs ¼ 0:33bÞ: Q1 The path in tissue of the 2.2 MeV gamma rays generated in this reaction can be of several centimetres. It should be underlined that the reactor background contribution is low in BNCT neutron fields of a good quality. The spatial distribution of the dose due to photons and charged particles is different and therefore a reliable spatial imaging (or at least mapping or profiling) of these components is of primary importance. Dose images have been acquired in a cylindrical gel phantom irradiated both in the thermal column of the TRIGA thermal reactor and in the new thermal column (2) of the TAPIRO fast reactor of ENEA (Casaccia, Rome). The volume of the gel phantom is about that of a human liver. Dose profiles have been calculated in the phantom for the same irradiation conditions. EXPERIMENTAL METHODS AND MATERIALS In-phantom imaging was performed by means of the optical analysis of gel dosemeters, allowing to separate the various components of the absorbed 85 90 95 100 105 110 # The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

115 120 125 130 135 dose by means of properly developed modalities (3 5). In this work, gel dosemeters were designed with the aim of detecting large dose images across suitably composed phantoms. Such dosemeters consist of 3 mm thick gel layers of a convenient shape. Phantom design In both the reactor columns, the same cylindrical (11 cm in diameter and 12 cm in height) phantoms were utilised for dose measurements. The phantoms consist of two half-cylinders of tissue-equivalent (TE) gel contained in a thin polyethylene shell (1 mm thick). Squared dosemeters (12 12 cm 2 ) were inserted between the two half-cylinders, like in a sandwich. In both reactors, the phantom was exposed with the cylinder axis normal to the one of the reactor core. The phantom placed in the thermal column of the TAPIRO reactor is sketched in Figure 1. Two kinds of phantoms were prepared: one containing TE gel and the other with a similar TE gel containing 15 ppm of 10 B. The same set of measurements was carried out at each reactor. G. GAMBARINI ET AL. to ferric ions and the conversion yield is proportional to the absorbed dose (until saturation). XO induces visible light absorption at about 585 nm. Dosemeter analysis consists in measurements of visible light transmission around 585 nm, imaged with a CCD camera. The absorbed dose is linearly correlated to the difference of optical density, obtained from pixel-to-pixel elaboration of the grey-level images detected before and after irradiation. The composition of the gel dosemeters is: gelatin from porcine skin [C 17 H 32 N 5 O 6 ] x (weight fraction 3%), ferrous sulphate solution [1 mm Fe(NH 4 ) 2 (SO 4 ) 2 6H 2 O], sulphuric acid [25 mm H 2 SO 4 ] and XO [0.165 mm C 31 H 27 N 2 Na 5 O 13 S]. This composition gives a good tissue equivalence of the gel matrix. In order to separate boron dose, some dosemeters were prepared adding an appropriate amount of boric acid (H 3 BO 3 ) in order to have the desired percentage of 10 B. For the inter-comparison with the gel dosemeter results, also measurements of the neutron fluence rate were carried out, utilising bare and cadmiumcovered Au foils. 175 180 185 190 195 140 Gel dosemeters The dosemeters utilised in this work were Fricke gels (Fricke-Xylenol-Orange-Infused gels), prepared in laboratory by incorporating in a gelatinous matrix a solution of ferrous sulphate and sulphuric acid (which is the main component of the standard Fricke dosemeter) and the Xylenol Orange (XO) compound. The gelling agent is (C 17 H 32 N 5 O 6 ) x. Ionising radiation causes conversion of ferrous ions 145 150 MONTE CARLO SIMULATIONS Dose calculations were performed with Monte Carlo (MC) simulations. The MCNPX 2.5.0 code was employed to calculate the dose distributions for the TAPIRO reactor, whereas the MCNP code (version 4C) was utilised for the TRIGA reactor. Particular attention was given to reproduce strictly the geometry and the composition of the reactors in order to improve the accuracy of the simulation results. The composition and the geometry of the phantom were simulated according to the experimental ones. 200 205 210 155 160 165 170 Figure 1. Geometrical arrangement for the MC simulation of the TAPIRO. The reactor core is shown in the figure as the black square on the right and, on the left, the thermal column is visible with the phantom containing the dosemeters. TRIGA reactor As mentioned earlier, the simulations were performed by using the MC transport code MCNP (version 4C). The geometry and the whole structure of the reactor TRIGA MARK II of University of Pavia were coded in detail in the input file. Many tests were performed and the computed gamma dose and neutron fluence rates were in good agreement with the experimental data. The phantom was placed inside the reactor thermal column at the same position of the experimental setup. Owing to the MCNP capability to build repeated structures, the phantom was divided into voxels of 1 1 0.3 cm 3 in volume. The gamma dose and the charged particle contribution to the dose were evaluated separately. 215 220 225 Page 2 of 5

230 235 240 245 250 255 260 265 TAPIRO reactor The dose calculations for the TAPIRO reactor were performed with MCNPX 2.5.0. The neutron fluence rate was scored inside the gel-phantom placed inside the thermal column of the TAPIRO reactor (2). The simulations were performed by adding the cylindrical gel-phantom to the TAPIRO reactor scheme adopted in previous works (2), referring to the following configurations: (1) PH-S: phantom consisting of the gel matrix only and (2) PH-B: phantom consisting of the gel matrix containing 15 ppm of 10 B. Two gel-layer dosemeters, one without boron and the other containing 36 ppm of 10 B, were placed adjacently in the central plane of the phantoms. All the calculations were performed with the aim of determining the dose distribution in a dosemeter central zone of dimensions 11 cm 2cm 0.3 cm. For this purpose, the scoring volume was subdivided into 1 cm wide voxels. Therefore, the scored dose values are averaged over a region (voxel) with dimensions 1 cm 2cm 0.3 cm ¼ 0.6 cm 3. The geometric arrangement is shown in Figure 1. RESULTS Gamma dose images were assessed with calibrated dosemeters having the standard composition (standard gel dosemeteres). The dose due to the charged particles generated by thermal neutrons on 10 B (boron dose) was obtained from the dose images of standard and borated gel dosemeters, irradiated adjacently in the phantom. These images were GEL DOSIMETRY IN REACTOR THERMAL COLUMNS Figure 3. Spatial distribution of the boron dose obtained by pixel-to-pixel elaboration of the dose images shown in Figure 2. attained by utilising the calibration factors of the two kinds of gel dosemeters. The contribution of boron dose was assessed from the pixel-to-pixel difference of standard and boron loaded dosemeters. These differences were multiplyed by a coefficient that takes into account the lower sensitivity (41%) of the gel dosemeters to the charged particles generated by 10 B reactions. Figure 2 shows the spatial distributions obtained with (a) the standard and (b) the borated gel dosemeters exposed in the central plane of the standard phantom exposed in the TRIGA thermal column. Figure 3 shows the boron dose deduced from the two images of Figure 2. The shape of the spatial distribution of the boron dose is very similar to the one calculated with MC simulations in the TAPIRO thermal column (Figure 4). The gamma and boron dose profiles measured in the central axis of the phantom are shown in 290 295 300 305 310 315 320 325 270 330 275 335 280 285 Figure 2. Spatial distributions obtained from dose images detected by means of (a) standard and (b) borated gel dosemeters irradiated in the central plane of the standard phantom exposed in the thermal column of the TRIGA reactor. Figure 4. Spatial distribution of the boron dose for the central plane of the standard phantom exposed in the thermal column of the TAPIRO reactor, obtained by MC simulations. 340 Page 3 of 5

G. GAMBARINI ET AL. 400 345 405 350 410 355 415 360 Figure 5. Depth profiles of gamma and 10 B (40 ppm) dose rates in standard and boron (15 ppm) loaded phantoms. Continuous lines are the profiles extracted from the images of gel dosimeters and dotted lines are the fitting curves. Points are 10 B doses evaluated from the fluence rates measured with activation foils. 420 365 370 375 Figures 5 and 6 for the TRIGA and the TAPIRO reactor, respectively. The results obtained by means of activation foils and by MC calculations are also shown in the same figures. Finally, to show the effect of the variation of the amount of 10 B on neutron fluence rate, the results obtained with activation techniques in the two phantoms Ph S and Ph B are shown in Figure 7 a and b for TAPIRO and TRIGA reactors, respectively. value in the central region of the irradiated volume, respectively. Finally, the variation of the concentration of boron in healthy tissue has a fairly slight effect on the shape of the dose distribution, as it can be 425 430 CONCLUSIONS 435 380 The results obtained in the the two thermal columns considered in this work are very similar. The spatial distribution of the boron and the gamma dose show a minimum and a maximum 440 385 445 390 450 395 Figure 6. Depth-dose profiles in phantoms with or without 15 ppm of 10 B, exposed in the thermal column of TAPIRO reactor. Figure 7. Themal neutron fluence rate versus depth in the Ph S and Ph B phantoms exposed in the thermal column of the TAPIRO (a) and of the TRIGA (b) reactors. 455 Page 4 of 5

460 465 470 observed in Figure 7. This implies that the level of accuracy at which the boron concentration is usually assessed in treatments may be sufficient. ACKNOWLEDGEMENTS The work was partially supported by INFN (Italy) and partially by MURST (Prot. 2001062789_002). GEL DOSIMETRY IN REACTOR THERMAL COLUMNS REFERENCES 1. Pinelli, T., Zonta, A., Altieri, S., Barni, S., Brughieri, A., Pedroni, P., Bruschi, P., Chiari, P., Ferrari, C. and Zonta, C. TAOrMINA: From the First Idea to the ApplicationtotheHumanLiver. Proceedings of the 10th Int Symposium on Neutron Capture Therapy for Cancer, (Bologna: Monduzzi Editore) pp. 1065 1072 (2002). 2. Esposito, J., Agosteo, S. and Rosi, G. The new hybrid thermal neutron facility at TAPIRO reactor for BNCT 515 radiobiological experiments, Proceedings of the NEUDOS-10, Uppsala, Sweden, 12 16 June 2005 (to be issued on Radiat. Prot. Dosim.). Q2 3. Gambarini, G., Agosteo, S., Danesi, U., Garbellini, F., Lietti, B., Mauri, M. and Rosi, G. Imaging and Profiling of Absorbed Dose in Neutron Capture Therapy. IEEE 520 Trans. Nucl. Sci. 48, 780 784 (2001). 4. Gambarini, G., Birattari, C., Colombi, C., Pirola L. and Rosi, G. Fricke-Gel Dosimetry in Boron Neutron Capture Therapy. Rad. Protect. Dos. 101, 419 (2002). 525 5. Gambarini, G., Colli, V., Gay, S., Petrovich, C., Pirola, L. and Rosi, G. In-phantom imaging of all dose components in boron neutron capture therapy (BNCT) by means of gel dosimeters. Applied Radiation and Isotopes 61, 759 (2004). 530 475 535 480 540 485 545 490 550 495 555 500 560 505 565 510 570 Page 5 of 5