E. Bisceglie

N. Colonna

P. Colangelo

SANTORELLI, PIETRO

V. Paticchio

V. Variale

Bisceglie, E.

Colangelo, P.

Colonna, N.

Paticchio, V.

Santorelli, Pietro

Variale, V.

Archivio della ricerca - Università degli studi di Napoli Federico II

Production of epithermal neutron beams for BNCT

Nuclear Instruments and Methods in Physics Research A 476 (2002) 123–126Production of epithermal neutron beams for BNCTE. Biscegliea, P. Colangeloa, N. Colonnaa,*, V. Paticchioa,P. Santorellib, V. Varialeaa Istituto Nazione Fisica Nucleare, Sezione di Bari, Via Amendola 173, I-70126 Bari, ItalybDipartimento di Scienze Fisiche, Universit "a Federico II e INFN, I-80125 Napoli, ItalyAbstractThe use of boron neutron capture therapy (BNCT) for the treatment of deep-seated tumors requires neutron beamsof suitable energy and intensity. Simulations indicate the optimal energy to reside in the epithermal region, in particularbetween 1 and 10 keV. Therapeutic neutron beams with high spectral purity in this energy range could be produced withaccelerator-based neutron sources through a suitable neutron-producing reaction. Herein, we report on diﬀerentsolutions that have been investigated as possible sources of epithermal neutron beams for BNCT. The potential use ofsuch sources for a hospital-based therapeutic facility is discussed. r 2002 Elsevier Science B.V. All rights reserved.1. IntroductionBNCT is a two-component therapeutic modalitycurrently considered for the treatment of a numberof malignant tumors resistant to other chemo- andradiotherapeutic methods. In particular, this kindof hadrontherapy could reveal useful in thetreatment of Glioblastoma Multiforme (GBM),an aggressive type of brain cancer [1]. The methodis based on the radiation damage produced by highLET particles emitted in the 10B neutron capturereaction 10B(n,a)7Li. To obtain a high tumorcontrol probability with minimal collateral eﬀectson healthy tissues, an adequate concentration of10B has to selectively accumulate in the tumor cellsby means of speciﬁc borated compounds. Thepatient is then irradiated with neutron beams ofenergy and intensity suitably chosen so that amaximum density of thermal neutrons is reachedin the proximity of the tumor area.Clinical BNCT trials are currently undergoingat nuclear reactors; however, the development ofhigh intensity accelerators could lead to high-quality, safe, and cost-eﬀective epithermal neutronsources for BNCT (see for example Ref. [2]). Infact, compared to nuclear reactors, accelerator-based sources may allow to produce epithermalneutron beams with higher spectral purity andlower contamination of g-rays, and the use of low-energy accelerators may enable the operation ofBNCT facilities in metropolitan areas.We report on a study of diﬀerent neutronproducing reactions that could be used in con-junction with high-current accelerators, to produceepithermal neutron beams for BNCT. The mainfeatures of the reactions and the requirements ofthe primary particle beam are presented anddiscussed, in particular, regarding the potentialuse of such sources in hospital-based BNCTfacilities.*Corresponding author. Tel.: +39-80-544-2351; fax: +39-80-544-2470.E-mail address: nicola.colonna@ba.infn.it (N. Colonna).0168-9002/02/$ -see front matter r 2002 Elsevier Science B.V. All rights reserved.PII: S 0 1 6 8 - 9 0 0 2 ( 0 1 ) 0 1 4 0 6 - 12. Optimal energy of therapeutic neutronsThe optimal energy of a neutron beam for thetreatment of deep-seated tumors can be investi-gated by means of simulations of the dosedeposition in tissues. To this end, we have usedthe GEANT/Micap package [3]. A realistic de-scription of the geometry and of the headcomposition was used, with a tumor region locatedat 5 cm depth inside the brain. In the simulations,10B was speciﬁcally included in normal and tumortissues, in concentrations of 10 and 43 parts-per-million respectively. These loading are typical ofBPA, a 10B-carrier currently used in clinical trials.RBE values of 1.6 and 2.3 were chosen for protonsand a-particles, respectively.The quality of the neutron beam was assessed byanalyzing several ﬁgures of merit of the simulateddose distribution, as a function of the neutronenergy. Fig. 1a shows the therapeutic gain (TG),deﬁned as the ratio between the dose released tothe tumor and the maximum dose to normaltissues, for a tumor depth of 5 (solid symbols) and8 cm (open symbols). One observes that theoptimal neutron energy for the considered tumorlocation and 10B concentration is between 1 and10 keV. Neutrons of lower energy thermalize atdepths smaller than the tumor location, while forhigher energies, recoiling protons lead to a sharpincrease of the dose released to the normal tissues,in particular, to the skin and at the brain surface.The depth-dose proﬁle in brain is shown in Fig. 1bfor a 4 keV neutron beam.Although monoenergetic neutron beams withenergies of 1–10 keV cannot be readily produced,one should try to approach such a condition inorder to optimize the therapeutic eﬀect. In the caseof reactor-based sources, the energy distribution ofthe neutron beam can be optimized by anappropriate choice of the material and geometryof the beam shaping assembly. A large improve-ment in the quality of the epithermal neutronbeam could be achieved by using an acceleratorand a suitable proton- or deuteron-induced reac-tion for neutron production. The choice of thebeam energy and of the target is mainly dictatedby the need of a high yield of low-energy neutrons(Eno1MeV), and a small contamination of high-energy neutron and g-rays. Furthermore, the sizeand cost of the accelerator could be minimized bychoosing a low energy for the primary beam, whilethe target should present good mechanical andthermal properties. Finally, a stable residue shouldbe produced in the reaction, to reduce safetyproblems associated with storage and disposal ofthe targets.Several approaches can be used in the choice ofthe primary beam energy and conversion target.Various proposed solutions rely on the use of the7Li(p,n)7Be reaction at energy EpB2:5MeV or onthe 7Be(p,n)7B reaction at Ep > 3MeV [4,5]). Forthese reactions, the proton beam current needed toFig. 1. (a) Ratio between the BNCT dose released to tumor andthe maximum dose to normal tissues as a function of neutronenergy. (b) Depth-dose distribution in the brain for a neutronbeam of 4 keV energy. The symbols represent the total dose,while the dashed curves depict the partial doses produced by thevarious reactions occurring in biological tissues (n–p elasticscattering, the 1H(n,g)2H, the 14N(n,p)14C and the 10B(n,a)7Licapture reactions).E. Bisceglie et al. / Nuclear Instruments and Methods in Physics Research A 476 (2002) 123–126124produce neutron ﬂuences adequate for the therapyranges from 1–30mA, depending on the requiredquality of the therapeutic neutron beam. The useof the Li(p,n) reaction, however, is complicated bythe low melting point of the target (1701) and bythe production of the radioactive 7Be residue. Onthe other hand, the Be target is useful only at arelatively higher proton energy. For this reason,alternative approaches for the production ofepithermal neutrons are being investigated.3. Neutron-producing reactions at low energyA promising approach is represented by (d; n)reactions at low energy. Most of these reactionspresent a positive Q-value, which in principleallows for the use of deuteron beams of energy aslow as 1MeV. To investigate the feasibility of thislatter approach, we have performed a systematicstudy of the yield, energy and angular distributionof neutrons emitted in low-energy (d;n) reactions[6]. The measurements were performed at the 8800Cyclotron of Lawrence Berkeley National Labora-tory, USA, in collaboration with groups from theNuclear Science and Life Science Divisions ofLBNL. The setup used in the measurementsconsisted of ﬁve liquid scintillator cells, with n=gdiscrimination properties and a minimum thresh-old of 100 keV on the neutron energy, recon-structed by time-of-ﬂight relative to the cyclotronRF. Among the diﬀerent targets investigated atdeuteron energies Edo2MeV, only 9Be and 13Cpresent a yield suﬃciently high to be of interest forthe production of epithermal neutrons for BNCT,with the Be target producing neutrons almost afactor of 2 greater than that produced by 13C.Fig. 2 shows the energy distribution and TOFspectrum for both targets. Due to the largecontamination of high energy neutrons, the9Be(d,n) reaction does not produce epithermalneutrons with the intensity and spectral character-istics adequate for BNCT. On the contrary, therelatively large-yield and low-contamination ofhigh-energy neutrons make the 13C(d,n)14N reac-tion at Ed ¼ 1:5MeV potentially interesting for ahospital-based facility, thanks also to the goodthermal and mechanical properties of the C targetand the low-energy of the primary beam, whichwould result in a relatively simple and inexpensiveaccelerator. The solid histogram in Fig. 3 repre-sents the spectrum of epithermal neutrons thatwould be produced by the 13C(d,n)14N reactionwith a moderator of LiF 25 cm thick, a reﬂector ofAl2O3, a delimiter of lithiated polyethilene and an6Li layer for thermal neutron ﬁltering. The currentrequired for a treatment time of 15min wasestimated for this reaction to be around 100mA,a value within reach of the high-intensity accel-erator technology currently being developed.Finally, a class of suitable neutron sources isrepresented by the near-threshold reactions. In thiscase, the low-yield of neutrons is compensated byFig. 2. Eﬃciency-corrected energy spectrum and time-of-ﬂightdistributions (inside panel) of neutron emitted in the13C(d,n)14N (panel a) and 9Be(d,n)10B reactions (panel b), atan incident energy of 1.5MeV. The threshold on the lightoutput of the scintillator cells was kept to 10 keV electron-equivalent, corresponding to a neutron energy threshold of100 keV.E. Bisceglie et al. / Nuclear Instruments and Methods in Physics Research A 476 (2002) 123–126 125their low-energy permitting moderation for clinicalapplication. The dashed histogram in Fig. 3 showsthe epithermal neutron spectrum that can beproduced with the 7Li(p,n) reaction at 1.95MeV,and with a beam shaping assembly comprised of8 cm thick BeO and a Pb reﬂector. The use of thisreaction requires an estimated proton beamcurrent of 5mA. Such an intense beam couldbecome feasible with commercial accelerators orwith the high-current RFQs like the one presentlybeing developed at the INFN Laboratori Nazio-nali Legnaro within the TRASCO project.In conclusion, among the diﬀerent reactionsstudied, the 13C(d,n) and the near-thresholdLi(p,n) reactions represent, in our opinion, themost interesting solutions for a hospital-basedBNCT facility. This is due in part to the relativelylow-cost and small-size of the accelerator. Beforehigh-intensity accelerators become available, how-ever, higher-energy reactions might more conve-niently be used in conjunction with the presentlyavailable research accelerators, to produce neutronbeams for in vitro or animal studies on BNCT.References[1] R.F. Barth, A.H. Soloway, R.M. Brugger, Cancer Invest. 14(1996) 534.[2] W.T. Chu, Proceedings of the Seventh InternationalSymposium on Neutron Capture Therapy for Cancer,Zurich, Switzerland, Septemper 1996.[3] E. Bisceglie, et al., Phys. Med. Biol. 45 (2000) 49.[4] D. Bleuel, et al., Med. Phys. 25 (1998) 1725.[5] G. Yue, et al., Med. Phys. 24 (1997) 851.[6] N. Colonna, et al., Med. Phys. 26 (1999) 793.Fig. 3. Epithermal neutron energy spectra produced with the13C(d,n)14N and the near-threshold 7Li(p,n)7Be reactions. Theoptimal beam shaping assembly used for each reaction isindicated.E. Bisceglie et al. / Nuclear Instruments and Methods in Physics Research A 476 (2002) 123–126126

https://www.iris.unina.it/retrieve/handle/11588/412809/253328/2002-02.PDF

Production of epithermal neutron beams for BNCT

Abstract

Similar works

Full text

Available Versions

Archivio della ricerca - Università degli studi di Napoli Federico II

Archivio della ricerca - Università degli studi di Napoli Federico II