Two applications for neutron capture therapy of epithermal neutron beams calculated from the 7Li(p,n) reaction are discussed. In particular, i) for a proton beam of 1920 keV of a 30 mA, a neutron beam of adequate features for BNCT

is found at an angle of 80◦ from the forward direction; and ii) for a proton beam of 1910 keV, a neutron beam is obtained at the forward direction suitable for performing

radiobiology experiments for the determination of the biological weighting factors of the fast dose component in neutron capture therapy

Arias de Saavedra, F.

Esquinas, P. L.

Jiménez-Bonilla, P.

Pedrosa, M.

Porras, I.

Praena, J.

English

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DOI 10.1393/ncc/i2015-15179-9Colloquia: UCANS-VIL NUOVO CIMENTO 38 C (2015) 179Epithermal neutron beams from the 7Li(p,n) reaction nearthe threshold for neutron capture therapyI. Porras(1), J. Praena(1)(2), F. Arias de Saavedra(1), M. Pedrosa(1),P. L. Esquinas(3) and P. Jime´nez-Bonilla(2)(4)(1) Departamento de F´ısica Ato´mica, Molecular y Nuclear, Universidad de GranadaGranada, Spain(2) Centro Nacional de Aceleradores (CNA) - Sevilla, Spain(3) Department of Physics and Astronomy, University of British Columbia - Vancouver, Canada(4) Departamento de F´ısica Ato´mica, Molecular y Nuclear, Universidad de SevillaSevilla, Spainreceived 22 February 2016Summary. — Two applications for neutron capture therapy of epithermal neutronbeams calculated from the 7Li(p,n) reaction are discussed. In particular, i) for aproton beam of 1920 keV of a 30 mA, a neutron beam of adequate features for BNCTis found at an angle of 80◦ from the forward direction; and ii) for a proton beamof 1910 keV, a neutron beam is obtained at the forward direction suitable for per-forming radiobiology experiments for the determination of the biological weightingfactors of the fast dose component in neutron capture therapy.1. – DescriptionBoron Neutron Capture Therapy (BNCT) [1] is an experimental form of radiotherapybased on the selective uptake of a boron compound by tumor cells and the subsequentirradiation of the tumor with a low energy neutron beam producing a thermal neutronfield in the tumor. Thermal neutrons are captured by the boron atoms by means of a(n, α) reaction in which high-energy heavy charged particles are delivered locally to thetumor. These particles have a significantly higher linear energy transfer to the medium(tumor) than photons or electrons, and therefore are more biologically effective thanconventional radiotherapy. Up to now, all clinical trials of BNCT have been performedfrom research reactor neutron sources. These neutron sources are scarce and are notpractical for construction in hospitals. For this reason, accelerator-based neutron sources(ABNS) are in development in several countries, and in Kyoto (Japan), an ABNS is readyfor medical applications [2]. The ABNS in Japan is based on collisions of 30MeV protonsCreative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by/4.0) 12 I. PORRAS et al.from a cyclotron with a Be target. Another option, which requires a lower energy protonbeam, is based on the (p, n) reaction on 7Li near the threshold. This produces a lessenergetic neutron beam thus requiring minor moderation for use in patient irradiation [3].For BNCT, the spectrum of the neutron beam is critical. The neutrons should haveenough energy to penetrate deeply in the body, but not so high as to produce a largebackground radiation dose, while also being able to thermalize within the body. Thesefeatures require an initial epithermal spectrum for the neutrons, but the exact require-ments should be determined with Monte Carlo simulations.All the neutrons beams used in BNCT up to now have been obtained with somemoderation from the source, in order to obtain a spectrum in which more than 90% ofthe neutrons are in the epithermal range. This is defined as the interval [0.5 eV, 10 keV].However the upper bound is just a reference value and slightly greater energies canbe also suitable for BNCT. For example, it has been shown by MC simulation how amonoenergetic beam of 13.5 keV can be very appropriate for BNCT [4].The optimization of the neutron spectrum for BNCT is a question of compromise.Higher energies than 20 keV produce an undesirable maximum of the absorbed dose inthe surface of the phantom (which raises steeply when increasing the neutron energy),and energies below 1 keV would reduce strongly the penetrability of the beam in orderto reach deeper located tumors. The moderation of a neutron beam necessarily producea strong broadening of the spectrum. Our aim in this work is trying to obtain a neutronspectrum as close as possible to epithermal energies around 10 keV. For this purpose wehave analyzed the neutron spectrum obtained from the 7Li(p, n) reaction near the neutronproduction threshold (between 1.88MeV and 2MeV) and at certain angles from the beamdirection. Although the neutron yield reduces strongly when decreasing the proton energyfrom the 2.5MeV resonance, and also at increasing angles from the forward direction,the possibility of not needing moderation could be enough for certain BNCT applicationswhen a very high current accelerator (20–30mA) as those recently available is used.In this work we will perform calculations of an entire procedure for an accelerator-based BNCT application starting from the 7Li(p, n) reaction. We will explore, for protonenergies near the threshold and different exit angles, the possibility of obtaining anepithermal neutron spectrum which produces a depth-dose distribution in a body modelappropriate for a BNCT treatment. A second problem would be obtaining a suitablebeam for BNCT basic research (cell culture irradiation by epithermal neutrons), evenwith a low current accelerator. This is interesting for the experimental determination ofthe relative biological effectiveness (RBE) factors of epithermal neutrons.2. – MethodsThe form of the neutron spectrum as a function of the neutron energy and the exitangle, important ingredient in our simulations, is the thick target differential neutronyield that can be calculated asd2YdΩdEn(θ,En) = f7LidσpndΩ′dΩ′dΩdEpdEn1ndEpdx,(1a)where Ω(Ω′) is the solid angle in the laboratory (center of mass) system of reference,En(Ep) is the neutron (proton) energy in the laboratory system, f7Li = 0.925 is thefraction of 7Li in natural lithium metal (target composition), dσpndΩ′ is the differentialEPITHERMAL NEUTRON BEAMS FROM THE 7Li(p, n) REACTION ETC. 3cross section of the reaction in the center-of-mass system, n is the density of atoms inthe target and the whole denominator is the mass stopping power of protons in themedium.In the same way as Lee and Zhou [5], we have adjusted a cubic spline to the experi-mental data of the differential cross section from Lisken and Paulsen [6] and we have usedanalytical expressions for the mass stopping power [7]. Further details can be consultedin [5].2.1. A. Near threshold beam for BNCT . – With the neutron spectra obtained fromthese calculations, we have performed MC simulations using the MCNPX code, version2.5.0 [8]. For this application we have considered the geometry illustrated in fig. 1.The neutron field obtained from a proton beam of 1920 keV on a thick lithium targetis transported in a cylindrical phantom of 8 cm radius, 10 cm height. The material inthis cylinder is a representative soft tissue called 4-component soft tissue as definedby the International Commission on Radiation Units (ICRU) with the following masscomposition: 10.12% H, 76.18% O, 11.10% C and 2.60% N. The axis of the cylinder isplaced at an angle with respect to the proton beam direction of 80◦ and at a distanceof 5 cm. This situation has been selected from different choices of angles because it hasshown to be adequate for the depth-dose distribution inside the phantom.2.2. B. Epithermal beam for in-vitro radiobiology experiments. – The dose in a BNCTtreatment is usually decomposed in different contributions: boron, thermal (mainly dueto the protons emitted in the Nitrogen capture reaction), fast (mainly due to the recoilingprotons from elastic collisions of the neutrons at epithermal energies) and photon dose.Our goal is designing a method to evaluate separately the RBE factors of the fast andthermal dose for the same type of cells. The RBE factors are defined as the ratio betweenthe dose required for a photon irradiation and the actual field, producing both the samebiological effect.For obtaining these factors we can measure the biological effect after the irradiationwith two different neutron beams, one producing much more thermal than fast doseand another just the opposite. The former case happens under thermal beams as thoseobtained from reactors after neutron moderation. In this work we will design an exper-imental condition producing much more epithermal dose than thermal, which would bethe second case required.The situation studied, representing the irradiation of adherent cells, is the following:80oPhantomLi targetBeamFig. 1. – Schematics of the neutron irradiation of the cylindrical phantom of 8 cm radius, 10 cmheight. The distance between the phantom and the center of the Li target is 5 cm.4 I. PORRAS et al.BeamLi targetCulturemedium     CellsFig. 2. – Schematics of the neutron irradiation of culture cells. The dimensions are as follows:beam diameter 6mm, Li thick target of 2 cm diameter, distance target-cells 1 cm, diameter ofculture 2 cm, 1 cm water beyond the cells.the neutron field produced by a proton beam of 1910 keV (±1 keV) on a thick lithiumtarget is directed to a very thin layer of cells (represented by the same 4-componentICRU tissue). This cells are in a box of basis 6× 6 cm, and 2 cm height, filled by water(representing the culture medium). The situation is illustrated in fig. 2.3. – Results3.1. Application A. – The absorbed dose depth profile at the phantom axis is illus-trated in fig. 3. In both panels, the solid line corresponds to the tumor dose assuming aconcentration of boron of 40 ppm, while the dotted line, representing the normal tissuedose, is found assuming a concentration of 10 ppm. In the left panel, it is noticed howthe tumor absorbed dose is greater than the maximum of the normal tissue dose (hori-zontal dotted line) up to a depth of about 8 cm (advantage depth), and how in the rangebetween 2 and 5 cm depth, the tumor dose exceeds twice the maximum normal tissuedose (horizontal solid line). In the right panel the biological dose is estimated using theweighting factors of use in BNCT: 3.2 for the fast and thermal doses, 1.0 for the gammadose, and for the boron dose values of 3.8 (tumor) and 1.8 (normal tissue). We cansee in the plot the important enhancement of the weighted dose delivered to the tumorcompared to the normal tissue one.The results are illustrated for a reference proton beam intensity of 1mA. The lowdose rates obtained for this intensity are expected because the low neutron yield nearTumorNormal tissueTumorNormal tissuedepth in phantom (cm) depth in phantom (cm)Absorbed (physical) dose rate Weighted (biological) dose rateDose rate (mGy/min)  for 1 mA 02.04.06.0 8.0 10.0 12.0  1  2  3  4  5  6  7  8  9 10 02.5 0  1  2  3  4  5  6  7  8  9  104.03.5 3.02.01.5 1.0 0.5Fig. 3. – Absorbed (left) and weighted (right) dose rate depth profile in the phantom axis attumor cells (solid curve) and normal cells (dotted curve). The horizontal lines represent themaximum value of the normal tissue dose rate (dotted) and twice this value (solid).EPITHERMAL NEUTRON BEAMS FROM THE 7Li(p, n) REACTION ETC. 5Table I. – Dose rate components at the cell culture, for a proton beam of 1910 keV and a thickLi target for different beam currents.Component Gy/min (1mA) Gy/h (10μA)Df 1.370 0.822Dt 8.34× 10−4 5.00× 10−4the threshold and at this angle. However, with a high current accelerator (30mA) theweighted dose rate at the tumor could reach values between 10 and 20Gy/h (3.8Gy/hmaximum for normal tissue).The reason of the high differences between the tumor and normal tissue dose can beaddressed to the low values of the fast dose component, which is due to the low-energyspectrum of the neutrons. This is a difference with respect to previous calculations ofthe dose produced by this reaction in the forward direction, where a high peak at thesurface of the phantom usually appears due to the higher energy delivered by the mostenergetic neutrons in their first elastic collision in the medium.3.2. Application B . – The results of the MC calculation of the absorbed dose rateproduced at the cells represented by the disk of 2 cm in fig. 2 with the MCNPX codeabove mentioned are shown in table I. The fast dose component is much greater thanthe thermal one, which is the situation pursued. The values of the fast dose rate ishigh enough as to measure survival effects in cells (usually starting from 0.1Gy) in areasonable time, even if a low current accelerator (in the μA range) is available. Thismeasurements then would complement those performed with a thermal beam in whichthe situation is the opposite (in terms of relative dose contributions).4. – ConclusionsEpithermal neutron beams obtained from the 7Li(p, n) reaction near the thresholdcan be useful for neutron capture therapy, both for basic research and for therapy. Inthe first case, with an energy of the proton beam of 1910 keV, the neutron beam at theforward direction is adequate for radiobiology experiments even if the accelerator hasa low current. For the latter, in this work it has been analyzed a very simplistic case,but the results for a proton beam energy of 1920 keV and a phantom located at 80◦ arepromising. Therefore it seems interesting to research further in this direction with morerealistic calculations and experimentation.∗ ∗ ∗The authors acknowledge financial support from the Junta de Andaluc´ıa under projectP11-FQM-8229 and the CEI Biotic of the University of Granada (P-BS-64) and PlanEstatal 2013-2016 Retos FPA2013-47327-C2-1-R. M. Pedrosa acknowledges a grant underthe program Becas de Iniciacion a la Investigacio´n from the Universidad de Granada(Plan Propio de Investigacio´n).6 I. PORRAS et al.REFERENCES[1] Sauerwein W. A. G., Wittig A., Moss R. and Nakagawa Y., Neutron Capture Therapy:Principles and Applications (Springer-Verlag, Berlin) 2012.[2] Tanaka H., Sakurai Y., Suzuki M., Masunaga S. et al., Appl. Radiat. Isot., 69 (2011)1642.[3] Kobayashi T., Bengua G. Tanaka K. and Nakagawa Y., Phys. Med. Biol., 52 (2007)645.[4] Porras I., Appl. Radiat. Isot., 69 (2011) 1838.[5] Lee C. L. and Zhou X.-L., Nucl. Instrum. Methods Phys. Res. B, 152 (1999) 1.[6] Lisken H. and Paulsen A., At. Data Nucl. Data Tables, 15 (1975) 57.[7] Andersen H. H. and Ziegler J. F., Hydrogen: Stopping powers and ranges in all elements(Pergamon Press, New York) 1985.[8] Pelowitz D. B., MCNPX - User’s Manual, Version 2.5.0. Publication LACP-05-0369 (LosAlamos, NM, USA) 2005.

Epithermal neutron beams from the 7Li(p,n) reaction near

the threshold for neutron capture therapy

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Epithermal neutron beams from the 7Li(p,n) reaction near the threshold for neutron capture therapy

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