Journal of Instrumentation

OPEN ACCESS Related content

- Neutron medical treatment of tumours — a
Neutron beams implemented at nuclear research survey of facilities
F M Wagner, B Loeper-Kabasakal and H
reactors for BNCT Breitkreutz

- Design and dosimetric evaluation of beam

shaping assembly for BNCT of compact
To cite this article: E. Bavarnegin et al 2017 JINST 12 P05005 D–T neutron generator by Monte Carlo
simulation
G S Sahoo, S D Sharma, S P Tripathy et
al.

- Conceptual design of BNCT facility based

View the article online for updates and enhancements. on the TRR medical room
M. Golshanian, A.A. Rajabi and Y.
Kasesaz

Recent citations
- Neutronic feasibility study of using a
multipurpose MNSR for BNCT, neutron
radiography, and NAA
J. Mokhtari et al

- Gamma-ray and neutron shielding features

for some fast neutron moderators of
interest in 252Cf-based boron neutron
capture therapy
Nassreldeen A.A. Elsheikh

- Neutron radiobiology studies with a pure

cold neutron beam
M. Pedrosa-Rivera et al

This content was downloaded from IP address 186.155.14.192 on 05/05/2020 at 12:08

 Published by IOP Publishing for Sissa Medialab
Received: February 19, 2017
Accepted: April 27, 2017
Published: May 9, 2017

Neutron beams implemented at nuclear research reactors

2017 JINST 12 P05005

for BNCT

E. Bavarnegin,a Y. Kasesaza,1 and F.M. Wagnerb

a Reactor and nuclear safety research school, Nuclear Science and Technology Research Institute (NSTRI),
Tehran, Iran
b Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universität München,

85748 Garching, Germany

E-mail: ykasesaz@aeoi.org.ir

Abstract: This paper presents a survey of neutron beams which were or are in use at 56 Nuclear
Research Reactors (NRRs) in order to be used for BNCT, either for treatment or research purposes
in aspects of various combinations of materials that were used in their Beam Shaping Assembly
(BSA) design, use of fission converters and optimized beam parameters. All our knowledge about
BNCT is indebted to researches that have been done in NRRs. The results of about 60 years
research in BNCT and also the successes of this method in medical treatment of tumors show that,
for the development of BNCT as a routine cancer therapy method, hospital-based neutron sources
are needed. Achieving a physical data collection on BNCT neutron beams based on NRRs will be
helpful for beam designers in developing a non-reactor based neutron beam.

Keywords: Instrumentation for neutron sources; Instrumentation for particle-beam therapy

1Corresponding author.

Published under the terms of the Creative Commons Attribution 3.0 License by IOP
Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must doi:10.1088/1748-0221/12/05/P05005
maintain attribution to the author(s) and the published article’s title, journal citation and DOI.
Contents

1 Introduction 1

2 BNCT physical mechanism 2

3 The qualified neutron beam for BNCT 3

4 Beam Shaping Assembly (BSA) 4

2017 JINST 12 P05005

4.1 Moderator 4
4.2 Reflector 6
4.3 Reflector/moderator geometries 7
4.4 Fast neutrons, thermal neutrons and gamma filters 7
4.5 Fission converter technique 7

5 NRRs for BNCT 8

5.1 NRRs for BNCT in America 11
5.2 NRRs for BNCT in Asia 11
5.3 NRRs for BNCT in Europe 14

6 From reactors to accelerator-based BNCT 16

7 Conclusions 19

1 Introduction

In Boron Neutron Capture Theory (BNCT), the patient is injected with a tumor localizing drug
containing 10 B and then exposed to a suitable neutron beam. Boron captures thermal neutrons and
produces two high Linear Energy Transfer (LET) particles (4 He and 7 Li) that release their energy
within the cellular dimension, what is much more effective than low-LET radiation in deactivating
tumor cells [1].
BNCT relies on two key factors: a tumor selective boron carrier drug and a suitable neutron
source. Research in the area of development of boron-containing delivery agents for BNCT started
∼ 50 years ago. The other key to successfully administering BNCT is the neutron source. So far, the
only sources for BNCT have been Nuclear Research Reactors (NRRs). Interested readers are referred
to the book “Neutron Capture Therapy: Principles and Applications” by Prof. Dr. Sauerwein [2]
and also to two comprehensive review papers by R. Barth et al. [3, 4]. An old extensive summary of
the possibilities in neutron beam design, development and performance for BNCT was achieved in
an international workshop at MIT in 1990 [5]. Similarly, there are some other review papers [6–8].
The first clinical successes were reported by Prof. Dr. Hatanaka et al. [9, 10], later on a number
of other groups followed and proved positive effects on patients treated by BNCT [11–20]. After

–1–
about 60 years research and development on the reactor-based BNCT, the technical efforts are
focused on the accelerator-based neutron sources to be installed in hospitals [21–26].
BNCT requires neutron beams of suitable energy and intensity and low gamma background.
To achieve such a beam, a spectral Beam Shaping Assembly (BSA) must be designed and installed
between the neutron source and the patient [1] (see figure 3). The BSA generally consists of neutron
moderator, neutron reflector, thermal neutron filter, gamma filter, and collimator. The shapes,
dimensions and materials of a BSA are highly dependent on the neutron source specifications such
as mean energy and source strength.
This paper presents a survey of neutron beams which were or are in use at NRRs in order to
be used for BNCT, either for treatment or research purposes. The paper mainly will investigate 56

2017 JINST 12 P05005

NRRs with regard to various choice and combinations of their BSA materials, beam parameters
and the special use of nuclear fuel in BSA as a fission converter. Achieving a comprehensive data
collection on BNCT based on NRRs will be helpful for beam designers in developing a non-reactor
based neutron beam.

2 BNCT physical mechanism

Figure 1 shows a schematic view of what happens in BNCT. The fundamental reaction between
boron and thermal neutrons is:

nth + 10 B → 7 Li(0.84 MeV) + α(1.47 MeV) + γ(0.48 MeV) (93.7%) (2.1)

nth + 10 B → 7 Li(1.01 MeV) + α(1.78 MeV) (6.3%) (2.2)

Capturing a thermal neutron, 10 B promptly disintegrates in to two high LET particles: an alpha
particle and a recoiling lithium nucleus with 9 and 5 µm range in tissue, respectively [1].
The energy deposited by the 10 B(n,α)7 Li reaction is called the boron dose (DB ). In addition to
boron dose, three further main dose components are produced within the tissue in BNCT treatment.

Figure 1. BNCT cell-killing mechanism.

–2–
These principally undesired doses are generated by (1) incident and secondary gamma rays, Dγ ;
(2) the thermal neutron dose (DN ), i.e., the dose resulting mainly from thermal neutron capture in
nitrogen 14 N(nth ,p)14 C, and (3), the fast neutron dose (Dfn ), i.e., the dose from recoil protons [1]. The
total biologically weighted dose is the sum of these four dose components with the corresponding
weighting factors (wx ):
Dw = wγ Dγ + wB DB + wN DN + wfn Dfn (2.3)

Accepted values of the biological weighting factors are 1 for gamma dose, 3.2 for both thermal
and fast neutron dose, 3.8 for boron dose in tumor and 1.3 for boron dose in normal tissues,
respectively [1]. The goal of radiation therapy is to maximize tumor dose while minimizing

2017 JINST 12 P05005

exposure to normal tissue. Accordingly, the Therapeutic Gain (TG), i.e., the ratio between the
tumor dose and the maximum dose to the normal tissue has been defined. Higher TG means better
condition for therapy [1].

3 The qualified neutron beam for BNCT

In BNCT, an adequate thermal neutron field has to be created within the boron labeled tumor cells.
Figure 2 shows a comparison of thermal neutron flux-depth distributions for different incident
neutron energies [8].

Figure 2. Depth-distribution for monoenergetic neutron pencil beams of different energies [8].

As can be seen, an epithermal beam entering brain tissue creates a radiation field with a
maximum thermal flux at a depth of 2–3 cm, which drops exponentially thereafter. In contrast to the
epithermal beam, a thermal beam entering tissue falls off exponentially from the surface. The depth
distribution of the thermal field can be influenced by the incident neutron energy which is, however,
limited to a maximum of 10 keV; for higher neutron energies, the KERMA coefficient increases to
prohibitive values. This indicates that a thermal neutron beam is suitable for treatment of superficial
tumors, while for treatment of deep-seated tumors, only an epithermal neutron is suitable. In both,
epithermal and thermal BNCT neutron beams, fast neutrons and gamma rays are considered as the

–3–
beam contaminations which should be limited to the desired values. The required BNCT beam
parameters are presented in table 1 [27]. Beside thermal and epithermal entrance neutron beams,
the utilization of hyper-thermal neutrons (neutrons with energy range from 0.1 eV to 3 eV) was also
studied in order to improve the thermal neutron flux distribution at depth in a living body [10, 28].

Table 1. Neutron beam parameters recommended by the IAEA for BNCT [27].
Thermal BNCT Epithermal BNCT
Parameter Recommended value Parameter Recommended value
ϕthermal (cm−2 s−1 ) > 109 ϕepithermal (cm−2 s−1 ) > 109
ϕthermal /ϕtotal > 0.9 ϕepithermal /ϕthermal > 20

2017 JINST 12 P05005

D(epithermal+fast) /ϕthermal (Gycm2 ) < 2 × 10−13 Dfast /ϕepithermal (Gycm2 ) < 2 × 10−13
Dgamma /ϕthermal (Gycm2 ) < 2 × 10−13 Dgamma /ϕepithermal (Gycm2 ) < 2 × 10−13
Fast energy E > 10 keV
Epithermal energy 0.5 eV < E < 10 keV
Thermal energy E < 0.5 eV

4 Beam Shaping Assembly (BSA)

In order to apply BNCT successfully, the primary spectrum of the neutron source must be modified
to the required neutron beam (table 1) using an appropriate BSA. Figure 3 shows the schematic
view of a BSA. In this section different parts of BSA are introduced.

Figure 3. Schematic view of a common BSA.

4.1 Moderator
The fission neutron spectrum produced in a reactor core contains many fast neutrons. These fast
neutrons should be moderated and reach the desired epithermal energy range of about 0.5 eV to
10 keV. In epithermal BNCT, the moderator should have a high fast neutron scattering cross-section
( s,fast→epi ) and low epithermal neutron scattering and absorption cross-sections ( r,epi ) so that the
Í Í

value of s,fast→epi / r,epi parameter is as high as possible. As well, they should have a low fast
Í Í

neutron absorption cross-section because fast neutrons will be removed from the spectrum and
cannot contribute anymore to the lower energy regions. A good moderator also must not become
the source of a strong photon field and if so, the energies should behave low energies which can

–4–
be removed [1]. The macroscopic cross-sections of some candidate moderators which are used in
different BNCT facilities are presented in table 2 [29].

Table 2. Fast and epithermal cross-sections [cm−1 ] of some spectrum shifter materials [29].
Material AlF3 AlF3 /Al* MgF2 Al D2 O Ti V
0.340 0.247 0.351 0.112 0.259 0.204 0.364
Í
Ís,fast
0.268 0.186 0.308 0.080 0.322 0.269 0.447
Ís,epi
0.012 0.012 0.010 0.002 0.038 0.003 0.005
Ís,fast→epi
0.005 0.003 0.005 0.001 0.032 0.000 0.000
Ís,epi→th
0.013 0.012 0.011 0.002 0.039 0.003 0.005

2017 JINST 12 P05005

r,fast
0.005 0.004 0.005 0.001 0.032 0.005 0.010
Í
Í r,epi
s,fast→epi
Í 2.296 3.227 2.056 1.560 1.183 0.524 0.497
r,epi
*A 30% Al plus 70% Alf3 mixture

The moderators consisting of fluoride have the highest value of s,fast→epi / r,epi parameter,
Í Í

hence, fluoride has been considered as an important element as a moderator in BNCT. It has a
low neutron absorption cross-section and low energy threshold of inelastic scattering, as shown in
figure 4.

Figure 4. Neutron reaction cross-section of fluorine.

Especially, Fluental™ (Al 30% + AlF3 69% + LiF 1%) is a suitable neutron moderator material
developed at Technical Research Centre of Finland (VTT) [30]. It provides very good spectrum
shifting to the epithermal neutron region with a good fast neutron cutoff (figure 5 [31]).
Heavy water is another material that was used as a neutron moderator [32, 33]. In the JRR-4
reactor, four separate heavy water tanks were used to operate independently; thus, the optimum heavy
water thickness could be selected for both thermal and epithermal beams to meet the requirement
of various treatment depths. The tanks were installed along with a cadmium filter which was set to
change the beam condition from the thermal to the epithermal mode (figure 6 [33]).

–5–
 2017 JINST 12 P05005
Figure 5. Neutron flux per unit lethargy for different epithermal neutron filters at a TRIGA reactor [31].

Figure 6. The heavy water system and BSA in JRR-4 [33].

4.2 Reflector

Neutrons that initially are scattered in the moderator may leak out before reaching the energies
of interest. This loss can be substantially reduced by surrounding the moderator with a reflector.
The reflector returns neutrons that collide first in the moderator but leak out before slowing down
and also deflect neutrons that miss the moderator upon streaming from the source. In addition,
the (n,2n) reaction in the reflector contributes significantly to the total neutron production [34].
Some materials such as graphite [35], lead [36], BeO [37] and Tungsten/Molybdenum [38] have
been considered as neutron reflectors. Lead with low photon production and low cost is a preferred
reflector. Lead has also shown a better performance than graphite [36].

–6–
4.3 Reflector/moderator geometries
Generally, the reflector is considered as a layer which covers the moderator material, as shown in
figure 7. Kasesaz et al. proposed new reflector/moderator geometries including multi-layers and
hexagonal lattice. The effects of these geometries were investigated by MCNP4C Monte Carlo
code [39]. It was found that the proposed configurations have a significant effect to improve the
thermal to epithermal neutron flux ratio which is an important neutron beam parameter. Table 3
presents the values of neutron beam parameters related to some selected cases [39].

2017 JINST 12 P05005

Figure 7. Top view of four considered reflector/moderator configurations, red: reflector, green: modera-
tor [39].

Table 3. Values of neutron beam parameters related to some selected cases [39].
Geometry ϕepi ϕepi /ϕthermal Dfast /ϕepi
(10−7 cm−2 source particle) (10−13 Gycm2 )
A 12.5 35.1 0.151
B 16.7 24.7 0.120
C 13.9 222.2 1.571
D 11.6 427.7 1.775

4.4 Fast neutrons, thermal neutrons and gamma filters

In order to obtain an epithermal neutron beam with high quality, thermal and fast neutron filters
have to be used. The flux of fast neutrons can most effectively be decreased and transformed
to an epithermal flux by Al or its fluoric compounds [40]. Cadmium, Gadolinium, and materials
enriched with 10 B or 6 Li have high thermal cross-sections, but care must be taken about an additional
generation of gamma radiation (B, Gd, Cd) and of fast neutrons (Li). Figure 8 shows the total
neutron cross-section of these materials. In addition to thermal and fast neutrons, gamma rays
must be suppressed. Pb and Bi are the common gamma filters widely used in BNCT beam
lines [1, 27, 34, 41–43].

4.5 Fission converter technique

The fission converter approach is a method to convert thermal neutrons to fission neutrons. To do
this, e.g., arrays of nuclear fuel elements (fresh or spent fuel highly enriched in 235 U) are placed in

–7–
 2017 JINST 12 P05005
Figure 8. Total neutron cross-section of 10 B, 113m Cd and 6 Li.

the reactor thermal zone. Thermal neutrons in the thermal zone induce fission processes and thereby
fast neutrons which are then moderated and filtered to epithermal energy. Finally, a high intensity
epithermal neutron beam is produced close to the treatment position. Suitable fission converter
approach enable thermal research reactors to provide high intensity and high quality epithermal
neutron beams [2].
A lot of neutronic and engineering design studies are needed for having a fission converter-
based epithermal neutron beam. The first fission converter beam for BNCT was constructed at
the MITR [44]. W.S. Kiger III has performed the neutronic study of MITR for providing a fission
converter-based epithermal beam. After extensive studies on moderator, filter and collimator,
he proposed a beam with high epithermal neutron flux (about 1 × 1010 cm−2 s−1 at the patient
position), and low contaminations with fast neutrons and photons (less than 2 × 10−11 cGycm2 ) [45].
S. Sakamoto has performed further studies to provide a beam with better epithermal neutron flux
(1.91 × 1010 cm−2 s−1 ), low cost, enhanced safety and flexibility [46]. An engineering design
including satisfyingly steady state and accident criteria design were also performed [47]. Some
other fission converter-based beams were designed at BMRR [48], McClellan Nuclear Research
Center (MNRC) [49], MURR [50], MARIA [51], JSI [31], OSURR [52], MuITR [53] and KRR [54].
Figure 9 shows a plan view of some fission converter-based beam lines.

5 NRRs for BNCT

As mentioned above, NRRs were the first neutron sources used in clinical BNCT and a lot of
knowledge about BNCT has been derived from the experience in NRRs. Even low power NRRs
like TRIGA reactors can provide a sufficient neutron flux after appropriate adaptation.
A comprehensive data collection on BNCT based on NRRs will be helpful for beam designers
in developing a new neutron beam. There are 56 nuclear research reactors around the world that
have been used for BNCT, either for treatment or research purposes only. Table 4 presents the list
of these reactors.

–8–
 2017 JINST 12 P05005

Figure 9. Plan view of the some fission converter-based beam line at: (a) MIT [55], (b) BMRR [56],
(c) MNRC [49], (d) IMNSR [57].

–9–
 Table 4. List of all NRRs that have been considered for BNCT.
No. Reactor Country Power (MW) Ref.
1 BGRR U.S.A. 28 [58]
2 BMRR U.S.A. 3 [1]
3 BTU Hungary 0.1 [59]
4 BER-II Germany 10 [60]
5 Dalat Vietnam 0.5 [61]
6 DIDO U.K. 25 [62]
7 FiR-1 Finland 0.25 [63]
8 FRJ-2 Germany 23 [148]
9 FRM-I Germany 4 [64]
10 FRM-II Germany 20 [65]
11 FRMZ Germany 0.25 [66]

2017 JINST 12 P05005

12 GTRR U.S.A. 5 [67]
13 HANARO Korea 0.03 [68]
14 HFR Netherlands 45 [69]
15 HIFAR Australia 10 [147]
16 HTR Japan 0.1 [118]
17 IEA-R1 Brazil 5 [70]
18 IHNI China 0.03 [71]
19 IMNSR Iran 0.03 [27]
20 IRT MIFI Russia 2.5 [72]
21 IRT-Sofia Bulgaria 0.2 [73]
22 ISIS France 0.7 [149]
23 ITU Turkey 0.25 [74]
24 JRR-1 Japan 0.05 [151]
25 JRR-2 Japan 10 [118]
26 JRR-3 Japan 10 [118]
27 JRR-4 Japan 3.5 [33]
28 JSI Slovenia 0.25 [31]
29 KARTINI Indonesia 0.25 [75]
30 KRR Ukraine 10 [76]
31 KUR Japan 5 [77]
32 LENA Italy 0.25 [78]
33 LFR Netherlands 0.03 [79]
34 LVR-15 Czech republic 10 [80]
35 MARIA Poland 30 [40]
36 MINTR Malaysia 1 [81]
37 MITR U.S.A. 5 [82]
38 MNRC U.S.A. 2 [49]
39 MOATA Australia 0.1 [150]
40 MuITR Japan 0.1 [53]
41 MURR U.S.A. 10 [50]
42 OSTR U.S.A. 1 [83]
43 OSURR U.S.A. 0.5 [52]
44 PBF U.S.A. 20 [84]
45 R2-0 Sweden 1 [85]
46 RA-1 Argentina 0.04 [86]
47 RA-3 Argentina 10 [87]
48 RA-6 Argentina 0.5 [88]
49 RPI Portuguese 1 [89]
50 SMNSR Syria 0.03 [90]
51 TAPIRO Italy 0.05 [91]
52 THOR Taiwan 1 [92]
53 TRR Iran 5 [93]
54 WWR-K ALMATY Kazakhstan 6 [94]
55 WSU U.S.A. 1 [95]
56 YAYOI Japan 2 [96]

– 10 –
5.1 NRRs for BNCT in America

The first clinical trials of BNCT were performed at Brookhaven Graphite Research Reactor (BGRR)
in 1951 using beams of thermal neutrons [9]. A few years later, from 1959–1961, Brookhaven
Medical Research Reactor (BMRR) and Massachusetts Institute of Technology Reactor (MITR)
were designed and used for BNCT, and a series of patients were irradiated. In all cases, no survival
with BNCT was observed. The major problems were attributed to inadequate penetration of thermal
neutron beams, little known dose distribution, and lacking localization of boron in the tumor. As a
consequence, clinical trials of BNCT in U.S.A. were stopped [9, 97], but could be restarted in the
1990s at BMRR and MITR [98, 99]. The new epithermal beam with low fast neutron and gamma

2017 JINST 12 P05005

contaminations at MIT was able to penetrate the superficial tissues without causing too strong a
damage and to build up a thermal neutron field in deeper-seated tumor with sufficient intensity [99].
Experimental modality and research activities were also performed in (MNRC) [49], RA-6 [88],
RA-3 [87], OSTR [83], OSURR [52], PBF [84], RA-1 [86], GTRR [38] and WSU [95]. Table 5
represents the materials used in BSA structure of Americas BNCT facilities. The plan view of
some of these BSAs are presented in figure 10. The measured or calculated beams parameters are
presented in table 6.

Table 5. BSA materials used in BNCT beams in America (FC=Fission Converter).

Reactor BSA materials FC Ref.
BMRR Al/Al2 O3 /Cd/Bi/Pb/Li-Polyethylene Yes [5]
GTRR D2 O/Bi/Al/Al2 O3 /Pb/Cd/Li-Polyethylene/Concrete Yes [50]
MNRC Graphite/Al/AlF3 /Pb/Cd/Bi/Li-Polymer/LiF/Heavy concrete Yes [49]
MITR Al/PTEF/Cd/Pb Yes [82]
MURR Pb/Graphite/Al/Al2 O3 /Cd/Li-Polyethylene/High density concrete Yes [100]
OSTR D2 O/S/Li2 CO3 / No [83]
OSURR Al/Graphite/Lead/PbF2 /Cd/Concrete Yes [101]
RA-1 Al/Graphite/Cd No [86]
RA-3 Bi/Pb/Fe/Zircaloy-4/Cd/Paraffin No [87]
RA-6 Al/Al2 O3 /Pb/Cd/Bi/B-Polyethylene No [1]
WSU Pb/Al/Boral/Al2 O3 /Fluental/Bi/Li-Polyethylene/B-Polyethylene/Concrete No [1]

5.2 NRRs for BNCT in Asia

After the first failure in U.S.A., BNCT in Asia was pioneered by Japanese. It was started at
Hitachi Training Reactor (HTR) by Prof. Dr. Hatanaka [103] from 1968 to 1975 when this reactor
was closed permanently. Thereafter, Musashi Institute of Technology Research Reactor (MuITR)
was used for BNCT in Japan until 1989. This reactor was shut down because of a reactor pool
leakage [13]. Kyoto University Reactor (KUR) was another reactor in Japan which was established
in 1964. The first clinical study of BNCT at the thermal neutron irradiation facility of this reactor
was performed in May 1974 [32]. In the period from 1974 to 1995, only thermal neutron irradiations
could be delivered at this facility, hence, BNCT was applied in cases of malignant melanomas and
open-laid brain tumors only. From 1995 to 1996, the thermal neutron irradiation facility at the
KUR was remodeled and neutron energy spectra from almost pure thermal to epithermal became

– 11 –
 2017 JINST 12 P05005
Figure 10. Plan view of the some BSA in America: (a) BMRR [56], (b) MIT [55] (c) WSU [95], (d)
RA-6 [88].

Table 6. Calculated (C) or Measured (M) parameters of some American BNCT beams.
Reactor Mode M/C ϕthermal ϕepi ϕfast Dfast /ϕepi Ref.
(×10 cm s ) (×10 cm s ) (×10 cm s ) (×10−13 Gycm2 )
8 −2 −1 9 −2 −1 7 −2 −1

C 0.14 0.68 3 2.6

Epithermal
BMRR M 0.19 0.88 4.1 2.7 [102]
Thermal M 510 - - -
M 1.16 3.71 14 1
MITR Epithermal [102]
C 0.97 4.29 15.8 0.9
Epithermal C - 5 - 200
MNRC [49]
Thermal C 56 - - -
C 0.09 0.27 1.1 2.6
WSU Epithermal [102]
M 0.3 0.3 1.2 2.8
C 0.28 0.68 4.3 7.9
RA-6 Epithermal [102]
M 0.33 0.65 4.4 9.1
RA-3 Thermal M 9 - - - [87]

available [104]. In a clinical trial 23 children under 15 years were treated including 4 patients under
3 years [16].

– 12 –
 Japan Research Reactor No. 4 (JRR-4) is one of the other reactors which were used for BNCT.
Modification of JRR-4 for core conversion began in 1996, and its medical irradiation facility was
installed for BNCT and the reactor was adopted to generate epithermal as well as thermal neutron
beams. Clinical BNCT trials were started at JRR-4 in 1998 with the thermal neutron beam. At the
later stage of intraoperative BNCT (since 1999), the epithermal beam was used in JRR-4. However,
in December 2007, a crack in a graphite reflector of the reactor core was found on a weld of
the aluminum cladding. JRR-4 was stopped until February 2010 for replacement of the graphite
reflector. After restarting BNCT in 2010, 3 patients were treated.
Because of the March 2011 East Japan earthquake and tsunami, JRR-4 was stopped again with
no prospect of restarting [105].

2017 JINST 12 P05005

Another research reactor in Asia which has been used for BNCT is the Tsing Hua Open-
Pool Reactor (THOR). It is a 2 MW research reactor at National Tsing Hua University (NTHU)
in Hsinchu and is the only epithermal neutron source for BNCT research in Taiwan. The first
epithermal neutron beam of THOR was built in 1998. It was built by removing the removal portion
of the graphite blocks (see figure 11 [106]).

Figure 11. The horizontal cross-section of the THOR epithermal neutron beam [106].

The beam was used for conducting cell and animal experiments related to BNCT drug devel-
opments. THOR was shut down for renovation of a new epithermal neutron beam for BNCT in
January 2003. In November 2003, concrete cutting was finished for getting closer to the core and for
a larger treatment room. Figure 12a shows the top view of THOR new beam design [92]. Treatment
of patients was started in August of 2010 in this reactor. Up to September 2016, 22 patients were
treated [107].
Also IHNI in China has started human therapy with 6 patients up to December 2016 [108].
IHNI is the only reactor for BNCT which is installed at a hospital site.
Experiments and research activities were also performed in Syria [90], Indonesia [75],
Korea [68], Vietnam [61] Malaysia [81] and Iran [27, 41, 43, 93, 109–115].
Prof. Dr. A. Pazirandeh (from Tehran University) and Dr. M.K. Marashi (from NSTRI) initiated
BNCT research in Iran in 1990s. Their research was about the use of a beam tube of Tehran Research
Reactor (TRR) to produce a proper neutron beam for BNCT [109, 116, 117]. The results showed
that the final neutron flux was not sufficient for BNCT. Since then, no attempt was made to design a

– 13 –
proper neutron beam at TRR. In 2010, BNCT research has been restarted focusing on TRR thermal
column [41, 43, 93, 110], construction of a head phantom [111] and evaluation of beam parameters
inside of the phantom volume [112]. Simulations have shown that, an epithermal neutron beam can
be achieved at the thermal column exit if all graphite blocks are removed from the thermal column
and replaced by an appropriate BSA, but in practice, it was impossible to remove all graphite blocks
due to the high gamma dose caused by the reactor. So, the arrangement of graphite blocks has been
modified and a thermal neutron beam has been generated instead of epithermal neutron beam. More
details about the TRR BNCT project are provided in [93]. In addition to TRR, there are also some
MCNP design studies of thermal and epithermal neutron beams at the Isfahan Miniature Neutron
Source Reactor (IMNSR) [27, 57]. Table 7 shows the materials used in BSA of NRRs in Asia. The

2017 JINST 12 P05005

plan view of some BSAs in Asia are presented in figures 12 and 13. Some measured or calculated
beam parameters are presented in table 8.

Table 7. BSA materials used in BNCT beams in Asia (FC=Fission Converter).

Reactor BSA compositions FC Ref
HANARO Bi/Polyethylene/Cd/Si/Pb No [68]
IHNI Epithermal mode: Al/Al2 O3 /Pb/Bi/C, thermal mode: Bi/Pb/C/PE(Pb) No [71]
IMNSR H2 O/AlF3 /Al/Al2 O3 /Bi/Pb/Cd/Be/Air Yes [57]
IMNSR Epithermal mode: Be/Al/Fluental/Cd/Bi, thermal mode: Be/Al/CF2 /Bi/Pb No [27]
JRR-2 Graphite/Polyethylene/B4 C/Bi/LiF/Pb No [118]
JRR-4 Al/D2 O/Cd/Bi/Li-Polyethylene/B-Polyethylene No [1]
KARTINI Al/Ni/Bi/Li2 CO3 -Polyethylene/Barite concrete No [75]
KUR Al/D2 O/Bi/Pb/Polyethylene/B-Polyethylene/Cd No [77]
MuITR Al2 O3 /Bi/Pb/Concrete Yes [53]
SMNSR Al/Fluental/Bi/Li2 CO3 -Polyethylene/Cd/Pb No [90]
THOR Al/Fluental/Pb/Bi/Li-Polyethylene/Heavy concrete No [92]
TRR Pb/Graphite/Al/Bi/Cd/Concrete No [41]
TRR Pb/Graphite/Concrete/Boral No [43]
YAYOI Fe/Pb/Graphite/Bi/B-Paraffin/Polyethylene No [96]

5.3 NRRs for BNCT in Europe

The first European clinical trial of BNCT was carried out from 1997 to about 2003 at the Petten
High-Flux Reactor (HFR) in the Netherlands [1]. It used a transmission filter consisting mainly of
liquid Ar and therefore realized a concept completely different from the other reactors. The clinical
trials at Petten were followed by treatments at the TRIGA reactor FiR-1 in Finland [121], CZ
Check republic [80], Sweden [85] and Italy [91]. Biological and dosimetric research activities were
performed in Germany [122–124] U.K. [62], Portugal [89], Poland [40], Ukraine [76], Slovenia [31],
Bulgaria [73, 125] and Hungary [59].
FiR-1 reactor in Finland was a 250 kW TRIGA reactor which was, permanently closed after
more than 50 years of operation. Between 1999 and 2012, about 249 patients with head and neck
cancer, primary and recurrent brain tumors and melanoma were treated in this reactor [4]. Joensuu
et al. have reported on 18 patients with brain tumor. The results have supported continuation of
clinical research on BNCT [126]. Kankaanranta et al. has also reported on 30 patients with operable

– 14 –
 2017 JINST 12 P05005
Figure 12. Plan view of the some BSA in Asia: (a) THOR [92], (b) KUR [119], (c) IMNSR [27], (d) IHNI
[71], (e) TRR [43].

Table 8. Some Calculated (C) or Measured (M) parameters of Asian BNCT beams.
Reactor Mode M/C ϕthermal ϕepi ϕfast Dfast /ϕepi Ref.
(×108 cm−2 s−1 ) (×109 cm−2 s−1 ) (×107 cm−2 s−1 ) (×10−13 Gycm2 )
C 0.03 0.35 3.2 7.2
KUR Epithermal [102]
M 2.05 1.14 2.5 1.7
M 18 0.81 2.3 1.8
JRR-4 Hyper thermal [102]
C 16 0.64 1.9 2
THOR Epithermal M - 1.69 - 2.8 [92]
Thermal M 0.65 - 2.2 0.65 [41]
TRR
Epithermal C 5.6 - - - [43]
Epithermal C 0.156 0.4 3.6 5.6 [71]
IHNI
Thermal C 20.14 0.91 2.56 - [71]

– 15 –
 2017 JINST 12 P05005
Figure 13. Plan view of the some BSA in Asia: (a) Musashi [120], (b) YAYOI [96], (c) ITU [74], (d) Syria
[90], (e) IRT [73].

head and neck cancer. The results show that 76% of patients responded to BNCT, 21% of them had
tumor growth stabilization and 3% had progress [19, 20].
R2-0 research reactor in Sweden was another BNCT center in Europe. Capala et al. reported
about the treatment of 17 patients with brain tumor [127, 128]. The elemental compositions of each
reactor BNCT BSA are shown in table 9. The plan views of some BSAs in Europe are presented in
figure 14. Some measured or calculated beam parameters have been presented in table 10.

6 From reactors to accelerator-based BNCT

After gaining some experience in the different fields of BNCT during about 60 years, today’s ef-
forts to use BNCT as a routine radiotherapy focus on the hospital-based neutron sources such as
proton accelerator facility [21–26, 131–134], neutron generators [42, 135–137] and 252 Cf radioiso-
tope [138–140].

– 16 –
 Table 9. BSA materials used in BNCT beams in Europe (FC=Fission Converter).
Reactor BSA composition FC Ref.
BTU Graphite/Bi/Polyethylene No [59]
DIDO Al/S/Ar/B/Ti/Polyethylene/Pb/He/D2 O No [62]
FiR-1 Fluental/Boral/Bi/Pb/Li-Polyethylene/Al No [121]
HFR Cd/Al/Ti/S/Ar/Polyethylene/Pb/Heavy concrete No [69]
IRT-MIFI Graphite/Steel/Pb/Zirconium No [129]
IRT-Sofia Al/Al2 O3 /Graphite No [125]
JSI Graphite/Al/PbF2 /Fluental/Cd/Bi/Boral/Li2 Co3 -Polyethylene/Concrete Yes [31]
KRR Be/Fluental/Ni/B-Polyethylene Yes [76]

2017 JINST 12 P05005

LVR-15 Al/AlF3 /Pb/B-Polyethylene No [80]
MARIA Graphite/Pb/Al/AlF3 /Cd/Bi Yes [51]
R2-0 Al/Bi/Teflon/D2 O/Polyethylene B-Pb/Li No [130]
RPI Be/Al/Pb/Polyethylene/Concrete No [89]
TAPIRO AlF3 /Ni/Pb/Li-Polyethylene-Concrete No [91]

Figure 14. Plan view of the some BSA in Europe: (a) HFR [69], (b) DIDO [62], (c) FiR-1 [63],
(d) TAPIRO [91].

– 17 –
 Table 10. Calculated (C) or Measured (M) parameters of some European BNCT beams.
Reactor Mode M/C ϕthermal ϕepi ϕfast Dfast /ϕepi Ref.
(×108 cm−2 s−1 ) (×109 cm−2 s−1) (×107 cm−2 s−1 ) (×10−13 Gycm2 )
M 0.07 0.37 7.5 11
HFR Epithermal [102]
C 0.04 0.32 4.7 6.4
M 0.72 1.07 3.4 1.5
FiR-1 Epithermal [102]
C 0.66 1.03 3.2 1.4
LVR-15 Epithermal M 0.38 0.65 5.5 - [80]
TAPIRO Epithermal C 0.0566 3.02 51.9 6.5 [91]
KRR Epithermal C 0 3–5 - - [76]

2017 JINST 12 P05005

Neutron generators are devices which contain a compact linear accelerator. They can produce
neutrons using the reaction T(d,n)4 He or D(d,n)3 He. However, the d-T-reaction generates high
energy neutrons (14 MeV) which are difficult to moderate; and the d-D reaction does not deliver a
high neutron flux. Their advantages are the smallness of these neutron generators, their relatively
low price and the possibility to install them in a hospital environment [37, 42, 135, 141].
252 Cf sources need more frequent source replacement due to a short half-life of 2.6 years. It

decays either by alpha particle emission or by spontaneous fission with branching ratio of 96.9% to
3.1%, respectively. Furthermore, for BNCT a source of the order of 1 g would be needed which is
very difficult to obtain. A treatment trial in Thailand using 252 Cf interstitially for cervix carcinoma
in combination with boron could not be continued. Thus, the use of 252 Cf is not realistic [142, 143].
In contrast to reactors, accelerators can be easily turned on and off. Their operation and
management cost would be lower [2]. Recently Japanese unveiled several accelerator-based BNCT
facilities to treat tumors [144–146] — as an example, see figure 15. The main advantage of hospital-
based accelerators is related to their better acceptance by the clinicians in comparison with NRRs.
The main challenge in the use of accelerators for BNCT is that the particle current to create a
sufficient neutron flux should be greater than 10 mA which needs high technology components.
It is clear that the spectrum of neutrons generated in accelerator-based neutron sources must be
modified to obtain the required epithermal beam using a proper BSA.

Figure 15. Unveiled accelerator-based BNCT equipment at national cancer center in Tsukiji [145].

– 18 –
7 Conclusions

All our knowledge about BNCT is indebted to research made in NRRs. The results of about 60
years research in BNCT and also the demonstrated advantages of this method for treatment of
cancers show that to develop BNCT as a routine cancer therapy, a non-reactor based neutron source
is needed. Achieving a comprehensive data collection on BNCT based on NRRs will be helpful for
beam designers in developing a hospital-based neutron beam.

Acknowledgments

2017 JINST 12 P05005

The authors gratefully acknowledge the continuous support provided to us by Prof. Dr. Hossein
Khalafi, NSTRI, Tehran, Iran, Prof. Dr. Winfried Petry, MLZ Garching, Germany, and Prof. Dr. Rolf
Barth, Ohio State University, U.S.A.

References

[1] IAEA, Current Status of Neutron Capture Therapy, TECDOC-1223 (2001).

[2] W.A. Sauerwein et al., Neutron capture therapy: principles and applications, Springer Science
Business & Media (2012).
[3] R.F. Barth et al., Boron neutron capture therapy of cancer: current status and future prospects, Clin.
Canc. Res. 11 (2005) 3987.
[4] R.F. Barth et al., Current status of boron neutron capture therapy of high grade gliomas and
recurrent head and neck cancer, Radiat. Oncol. 7 (2012) 1.
[5] O.K. Harling, J.A. Bernard, R.C. Zamenhof eds., Neutron beam design, development and
performance for neutron capture therapy, Plenum Press, New York (1990).
[6] R.L. Moss, Review of Reactor-Based Neutron Beam Development for BNCT Applications, in
Advances in Neutron Capture Therapy, A.H. Soloway, R.F. Barth and D.E. Carpenter eds., Springer,
Boston, MA, U.S.A. (1993), pp. 1–7.
[7] O.K. Harling, Fission reactor based epithermal neutron irradiation facilities for routine clinical
application in BNCT — Hatanaka memorial lecture, Appl. Radiat. Isotopes 67 (2009) S7.
[8] F.M. Wagner, B. Loeper-Kabasakal and H. Breitkreutz, Neutron medical treatment of tumours — a
survey of facilities, 2012 JINST 7 C03041.
[9] D.N. Slatkin, A history of boron neutron capture therapy of brain tumours, Brain 114 (1991) 1609.
[10] W.H. Sweet, Early history of development of boron neutron capture therapy of tumors, Journal of
neuro-oncology 33 (1997) 19.
[11] S. González et al., First BNCT treatment of a skin melanoma in Argentina: dosimetric analysis and
clinical outcome, Appl. Radiat. Isotopes 61 (2004) 1101.
[12] D. Haritz, D. Gabel and R. Huiskamp, Clinical phase-I study of Na2B12H11SH (BSH) in patients
with malignant glioma as precondition for boron neutron capture therapy (BNCT), Int. J. Radiat.
Oncol. 28 (1994) 1175.
[13] Y. Oda et al., Clinical experience with BNCT for malignant brain tumors, in Advances in Neutron
Capture Therapy, Springer (1993), pp. 689–693.

– 19 –
[14] W.A. Sauerwein et al., Status report on the European clinical trial of BNCT at Petten (EORTC
protocol 11961), in Frontiers in Neutron Capture Therapy, Springer (2001), pp. 81–86.
[15] T. Yamamoto et al., Current clinical results of the Tsukuba BNCT trial, Appl. Radiat. Isotopes 61
(2004) 1089.
[16] Y. Nakagawa et al., Clinical results of BNCT for malignant brain tumors in children, Appl. Radiat.
Isotopes 67 (2009) S27.
[17] T. Kageji et al., Boron neutron capture therapy using mixed epithermal and thermal neutron beams
in patients with malignant glioma—correlation between radiation dose and radiation injury and
clinical outcome, Int. J. Radiat. Oncol. 65 (2006) 1446.

2017 JINST 12 P05005

[18] L. Wang et al., BNCT for locally recurrent head and neck cancer: preliminary clinical experience
from a phase I/II trial at Tsing Hua open-pool reactor, Appl. Radiat. Isotopes 69 (2011) 1803.
[19] L. Kankaanranta et al., Boron neutron capture therapy in the treatment of locally recurred head and
neck cancer, Int. J. Radiat. Oncol. 69 (2007) 475.
[20] L. Kankaanranta et al., Boron neutron capture therapy in the treatment of locally recurred
head-and-neck cancer: final analysis of a phase I/II trial, Int. J. Radiat. Oncol. 82 (2012) e67.
[21] A.J. Kreiner et al., Present status of accelerator-based BNCT, Rep. Practical Oncol. Radiother. 21
(2016) 95.
[22] C. Ceballos et al., Towards the final BSA modeling for the accelerator-driven BNCT facility at INFN
LNL, Appl. Radiat. Isotopes 69 (2011) 1660.
[23] H. Tanaka et al., Experimental verification of beam characteristics for cyclotron-based epithermal
neutron source (C-BENS), Appl. Radiat. Isotopes 69 (2011) 1642.
[24] T. Mitsumoto et al., Cyclotron-based neutron source for BNCT, in proceedings of Application of
accelerators in research and industry: Twenty-Second International Conference, 2013, pp. 319–322.
[25] V.T. Vento et al., Electrostatic design and beam transport for a folded tandem electrostatic
quadrupole accelerator facility for accelerator-based boron neutron capture therapy, Appl. Radiat.
Isotopes 69 (2011) 1649.
[26] M. Yoshioka et al., Construction of Accelerator-based BNCT Facility at Ibaraki Neutron Medical
Research Center, in proceedings of UCANS-IV, 2014.
[27] M. Monshizadeh et al., MCNP design of thermal and epithermal neutron beam for BNCT at the
Isfahan MNSR, Prog. Nucl. Energ. 83 (2015) 427.
[28] Y. Sakurai, T. Kobayashi and K. Kanda, A fundamental study on hyper-thermal neutrons for neutron
capture therapy, Phys. Med. Biol. 39 (1994) 2217.
[29] B. Montagnini et al., Spectrum shaping of accelerator-based neutron beams for BNCT, Nucl.
Instrum. Meth. 476 (2002) 90.
[30] P.H.I. Auterinen, Patent FI-92890 (1995).
[31] M. Maučec, Feasibility of the Utilization of BNCT in Thermalizing Column of TRIGA Reactor,
Springer (2001).
[32] K. Kanda et al., Thermal neutron standard field with a Maxwellian distribution using the KUR heavy
water facility, Nucl. Instrum. Meth. 148 (1978) 535.
[33] T. Nakamura et al., Resumption of JRR-4 and characteristics of neutron beam for BNCT, Appl.
Radiat. Isotopes 69 (2011) 1932.

– 20 –
[34] M. Asnal, T. Liamsuwan and T. Onjun, An evaluation on the design of beam shaping assembly based
on the DT reaction for BNCT, J. Phys. Conf. Ser. 611 (2015) 012031.
[35] A. Burlon et al., Optimization of a neutron production target and a beam shaping assembly based on
the 7 Li (p, n) 7 Be reaction for BNCT, Nucl. Instrum. Meth. B 229 (2005) 144.
[36] A. Burlon et al., An optimized neutron-beam shaping assembly for accelerator-based BNCT, Appl.
Radiat. Isotopes 61 (2004) 811.
[37] F.S. Rasouli, S.F. Masoudi and Y. Kasesaz, Design of a model for BSA to meet free beam parameters
for BNCT based on multiplier system for D-T neutron source, Ann. Nucl. Energy 39 (2012) 18.
[38] R. Uhlář et al., A new reflector structure for facility thermalizing D-T neutrons, J. Radioanal. Nucl.

2017 JINST 12 P05005

Chem. 300 (2014) 809.
[39] Y. Kasesaz, F. Rahmani and H. Khalafi, Investigation on the reflector/moderator geometry and its
effect on the neutron beam design in BNCT, Appl. Radiat. Isotopes 106 (2015) 34.
[40] K. Tyminska, Filter/moderator system for a BNCT beam of epithermal neutrons at nuclear reactor
MARIA, Pol. J. Med. Phys. Eng. 15 (2009) 77.
[41] Y. Kasesaz, H. Khalafi and F. Rahmani, Design of an epithermal neutron beam for BNCT in thermal
column of Tehran research reactor, Ann. Nucl. Energy 68 (2014) 234.
[42] Y. Kasesaz, H. Khalafi and F. Rahmani, Optimization of the beam shaping assembly in the D-D
neutron generators-based BNCT using the response matrix method, Appl. Radiat. Isotopes 82 (2013)
55.
[43] Y. Kasesaz et al., Design and construction of a thermal neutron beam for BNCT at Tehran Research
Reactor, Appl. Radiat. Isotopes 94 (2014) 149.
[44] O. Harling et al., The fission converter-based epithermal neutron irradiation facility at the
Massachusetts Institute of Technology reactor, Nucl. Sci. Eng. 140 (2002) 223.
[45] W. Kiger III, S. Sakamoto and O. Harling, Neutronic design of a fission converter-based epithermal
neutron beam for neutron capture therapy, Nucl. Sci. Eng. 131 (1999) 1.
[46] S. Sakamoto, W. Kiger III and O. Harling, Sensitivity studies of beam directionality, beam size and
neutron spectrum for a fission converter-based epithermal neutron beam for boron neutron capture
therapy, Med. Phys. 26 (1999) 1979.
[47] O. Harling et al., The new fission converter based epithermal neutron irradiation facility for neutron
capture therapy, Neutron News 12 (2001) 24.
[48] H.B. Liu et al., Design of a high-flux epithermal neutron beam using 235U fission plates at the
Brookhaven Medical Research Reactor, Med. Phys. 21 (1994) 1627.
[49] H. Liu et al., TRIGA®Fuel Based Converter Assembly Design for a Dual-Mode Neutron Beam
System at the McClellan Nuclear Radiation Center, in Frontiers in Neutron Capture Therapy,
Springer (2001), pp. 295–300.
[50] H.B. Liu and R.M. Brugger, A study of the concept of a fission-plate converter as a source for an
epithermal neutron beam, in Cancer Neutron Capture Therapy, Springer (1996), pp. 413–418.
[51] G. Tracz et al., Numerical optimisation of the fission-converter and the filter/moderator arrangement
for the Boron Neutron Capture Therapy, Nukleonika 48 (2003) 177.
[52] D.J. Turkoglu, Design, Construction and Characterization of an External Neutron Beam Facility at
The Ohio State University Nuclear Reactor Laboratory, Ohio State University (2012).

– 21 –
[53] T. Matsumoto, H.B. Liu and R.M. Brugger, Design studies of an epithermal neutron beam for
neutron capture therapy at the Musashi reactor, J. Nucl. Sci. Technol. 32 (1995) 87.
[54] O. Gritzay et al., Calculations of Neutron Source at the Kyiv Research Reactor for the Boron Neutron
Capture Therapy Aims, in proceedings of The Fifth International Conference on Nuclear and
Particle Physics, Cairo, Egypt, 2005, pp.275–280.
[55] K. Riley et al., The design, construction and performance of a variable collimator for epithermal
neutron capture therapy beams, Phys. Med. Biol. 49 (2004) 2015.
[56] H.B. Liu, R.M. Brugger and D.C. Rorer, Upgrades of the epithermal neutron beam at the Brookhaven
Medical Research Reactor, in Cancer Neutron Capture Therapy, Springer (1996), pp. 343–348.

2017 JINST 12 P05005

[57] J. Mokhtari et al., Conceptual design study of the low power and LEU medical reactor for BNCT
using in-tank fission converter to increase epithermal flux, Prog. Nucl. Energ. 95 (2017) 70.
[58] L. Farr, J. Robertson and E. Stickley, Physics and physiology of neutron-capture therapy, Proc. Natl.
Acad. Sci. U.S.A. 40 (1954) 1087.
[59] G. Csom, E. Zsolnay and E. Szondi, Investigation of neutron beams for the realization of boron
neutron capture therapy, in Neutron Beam Design, Development and Performance for Neutron
Capture Therapy, Springer, (1990), pp. 141–151.
[60] http://www-naweb.iaea.org, 2016.
[61] N.N. Dien and N.C. Hai, Status of neutron beam utilization at the Dalat nuclear research reactor,
2003.
[62] D. Ross et al., Designing an epithermal neutron beam for boron neutron capture therapy for a DIDO
type reactor using MCNP, Nucl. Instrum. Meth. A 334 (1993) 596.
[63] I. Auterinen et al., Metamorphosis of a 35 year-old TRIGA reactor into a modern BNCT facility, in
Frontiers in neutron capture therapy, Springer (2001), pp. 267–275.
[64] F.M. Wagner,et al., Reactor Neutron Therapy (RENT) Combined with Neutron Capture, in Second
International Symposium on Neutron Capture Therapy, Tokyo, Japan, 1985, pp. 223–227.
[65] T. Schmid et al., The effectiveness of the high-LET radiations from the boron neutron capture [10 B(n,
α)7 Li] reaction determined for induction of chromosome aberrations and apoptosis in lymphocytes
of human blood samples, Radiat. Environmen. Bioph. 54 (2015) 91.
[66] T. Schmitz et al., The alanine detector in BNCT dosimetry: Dose response in thermal and
epithermal neutron fields, Med. Phys. 42 (2015) 400.
[67] J. Russell Jr et al., Georgia Tech Research Reactor Epithermal Beam, in Neutron Beam Design,
Development and Performance for Neutron Capture Therapy, Springer (1990), pp. 219–227.
[68] M.S. Kim, S.J. Park and B.J. Jun, Measurements of in-phantom neutron flux distribution at the
HANARO BNCT facility, Nucl. Eng. Technol. 36 (2004) 203.
[69] R. Moss, Status of the BNCT project at the HFR Petten, in Cancer Neutron Capture Therapy,
Springer (1996), pp. 271–279.
[70] P. Coelho et al., Radiation field characterization of the NCT research facility at IEA-R1, in
proceedings of the 13th International Congress on Neutron Capture Therapy, 2008, 13682.
[71] G. Ke et al., The study of physics and thermal characteristics for in-hospital neutron irradiator
(IHNI), Appl. Radiat. Isotopes 67 (2009) S234.

– 22 –
[72] K. Zajtsev et al., Neutron capture therapy with thermal neutrons at IRT MIFI, Sov. Atom. Energy 91
(2001) 307.
[73] S. Belousov and K. Ilieva, Preliminary modeling of BNCT beam tube on IRT in Sofia, Appl. Radiat.
Isotopes 67 (2009) S230.
[74] Z. Akan et al., Modification of the radial beam port of ITU TRIGA Mark II research reactor for
BNCT applications, Appl. Radiat. Isotopes 99 (2015) 110.
[75] N. Fauziah, A. Widiharto and Y. Sardjono, A conceptual design of neutron collimator in the thermal
column of Kartini Research Reactor for in vitro and in vivo test of boron neutron capture therapy. ,
TRI DASA MEGA — Jurnal Teknologi Reaktor Nuklir 15 (2013) .

2017 JINST 12 P05005

[76] O. Gritzay et al., Monte-Carlo calculations for the development of a BNCT neutron source at the
Kyiv Research Reactor, Appl. Radiat. Isotopes 61 (2004) 869.
[77] T. Kobayashi et al., The Usage of the KUR Advanced Clinical Irradiation System for NCT under the
KUR Continous Operation, in Frontiers in Neutron Capture Therapy, Springer (2001), pp. 331–335.
[78] T. Pinelli et al., Development of a method to use boron neutron capture therapy for diffused tumours
of liver (TAORMINA project), in Cancer neutron capture therapy, Springer (1996), pp. 783–794.
[79] F. Stecher-Rasmussen et al., Development of the ECN Argonaut Reactor for BNCT Studies, in
Cancer Neutron Capture Therapy, Springer (1996), pp. 319-325.
[80] J. Burian et al., LVR-15 reactor epithermal neutron beam parameters — Results of measurements,
Appl. Radiat. Isotopes 67 (2009) S202.
[81] M.R.M. Solleh et al., Collimator and shielding design for boron neutron capture therapy (BNCT)
facility at TRIGA MARK II reactor, Journal of Nuclear and Related Technologies 8 (2011) 41.
[82] K. Riley, P. Binns and O. Harling, Performance characteristics of the MIT fission converter based
epithermal neutron beam, Phys. Med. Biol. 48 (2003) 943.
[83] K. Tiyapun, Epithermal neutron beam design at the Oregon State University TRIGA Mark II reactor
(OSTR) based on Monte Carlo methods, M.Sc. Thesis, Oregon Stae University (1997).
[84] F.J. Wheeler et al., Epithermal neutron beam design for neutron capture therapy at the Power Burst
Facility and the Brookhaven Medical Research Reactor, Nucl. Technol. 92 (1990) 106.
[85] V. Giusti, Computational design and preliminary measurements of a mixed-field irradiation facility,
Prog. Nucl. Energ. 50 (2008) 877.
[86] D.W. Nigg et al., Collaborative Physical and Biological Dosimetry Studies for Neutron Capture
Therapy at the RA-1 Research Reactor Facility, U.S. Department of Energy, Office of
Nonproliferation and National Security (2004).
[87] M. Miller et al., New irradiation facility for biomedical applications at the RA-3 reactor thermal
column, Appl. Radiat. Isotopes 67 (2009) S226.
[88] H. Blaumann et al., NCT Facility Development and Beam Characterisation at the RA-6 Reactor, in
Frontiers in Neutron Capture Therapy, Springer (2001), pp. 313–317.
[89] A. Ramalho et al., Preparation of a Beam Tube of the Portuguese Research Reactor to be Used in
BNC and Other Activites, in Frontiers in Neutron Capture Therapy, Springer (2001), pp. 307–311.
[90] I. Shaaban and M. Albarhoum, Design calculation of an epithermal neutronic beam for BNCT at the
Syrian MNSR using the MCNP4C code, Prog. Nucl. Energ. 78 (2015) 297.

– 23 –
 [91] K. Burn et al., The epithermal neutron beam for BNCT under construction at TAPIRO: Physics, J.
Phys. Conf. Ser. 41 (2006) 187.
[92] Y.-W. Liu et al., Renovation of epithermal neutron beam for BNCT at THOR, Appl. Radiat. Isotopes
61 (2004) 1039.
[93] Y. Kasesaz et al., BNCT project at Tehran Research Reactor: Current and prospective plans, Prog.
Nucl. Energ. 91 (2016) 107.
[94] F. Arinkin et al., Specific features of the WWR-K reactor horizontal channel as applied to BNCT, talk
given at 2textnd Eurasian Conference on Nuclear Science and its Application, 2002.
[95] D.W. Nigg et al., Flux and instrumentation upgrade for the epithermal neutron beam facility at

2017 JINST 12 P05005

Washington State University, Appl. Radiat. Isotopes 61 (2004) 993.
[96] Y. Oka, M. Akiyama and S. An, Study of epithermal neutron columns for boron neutron capture
therapy, Prog. Nucl. Energ. 32 (1998) 61.
[97] R. Moss et al., The requirements and development of neutron beams for neutron capture therapy of
brain cancer, Journal of Neuro-Oncology 33 (1997) 27.
[98] A.D. Chanana et al., Boron neutron capture therapy for glioblastoma multiforme: interim results
from the phase I/II dose-escalation studies, Neurosurgery 44 (1999) 1182.
[99] A.Z. Diaz, Assessment of the results from the phase I/II boron neutron capture therapy trials at the
Brookhaven National Laboratory from a clinician’s point of view, Journal of Neuro-Oncology 62
(2003) 101.
[100] Y. Mishima ed., Cancer Neutron Capture Therapy, Springer (2013).
[101] J.E. Woollard et al., A comparison of neutron beams for BNCT based on in-phantom neutron field
assessment parameters, Med. Phys. 28 (2001) 184.
[102] I. Auterinen et al., Measurement of free beam neutron spectra at eight BNCT facilities worldwide,
Appl. Radiat. Isotopes 61 (2004) 1021.
[103] H. Hatanaka, Clinical experience of boron neutron capture therapy for malignant brain tumors, in
proceedings of the First International Symposium on neutron capture therapy, Cambridge, MA,
U.S.A., October 12–14 1983, pp. 384–393.
[104] T. Kobayashi et al., The Remodeling and Basic Characteristics of the Heavy Water Neutron
Irradiation Facility of the Kyoto Univesity Research Reactor, Mainly for Neutron Capture Therapy,
Nucl. Technol. 131 (2000) 354.
[105] K. Nakai et al., Boron Neutron Capture Therapy for Glioblastoma: A Phase-I/II Clinical Trial at
JRR-4, European Association of Neuro-Oncology Magazine 4 (2014) 116.
[106] H.-M. Liu, P.-C. Hsu and T.-F. Liaw, Gamma dose measurement in a water phantom irradiated with
the BNCT facility at THOR, Radiat. Prot. Dosim. 95 (2001) 353.
[107] C.-K. Huang, C.-T. Liu and S. Jiang, Patient Activation Survey for BNCT Clinical Trials at THOR, in
Proceedings of the 17th International Congress on Neutron Capture Therapy, Columbia, Missouri,
U.S.A., October 2–7 2016.
[108] Z. Yong et al., Boron neutron capture therapy for malignant melanoma: first clinical case report in
China, Chin. J. Cancer Res. 28 (2016) 634.
[109] M.K. Marashi and A. Pazirandeh, The boron neutron capture therapy research facility at the Tehran
Research Reactor (TRR), in Cancer Neutron Capture Therapy, Springer (1996), pp. 327–335.

– 24 –
[110] Y. Kasesaz et al., A feasibility study of the Tehran research reactor as a neutron source for BNCT,
Appl. Radiat. Isotopes 90 (2014) 132.
[111] E. Bavarnegin et al., Construction of a head phantom for mixed neutron and gamma field dosimetry
in TRR, Measurement 89 (2016) 145.
[112] E. Bavarnegin et al., Measurement and simulation of the TRR BNCT beam parameters, Nucl.
Instrum. Meth. A 830 (2016) 53.
[113] E. Bavarnegin et al., Investigation of Dose Distribution in Mixed Neutron-Gamma Field of Boron
Neutron Capture Therapy using N-Isopropylacrylamide Gel, Nucl. Eng. Technol. 49 (2017) 189.
[114] E. Bavarnegin, A. Sadremomtaz and H. Khalafi, The three dimensional map of dose components in a

2017 JINST 12 P05005

head phantom for boron neutron capture therapy, Nucl. Technol. Radiat. 28 (2013) 273.
[115] H. Jarahi, Y. Kasesaz and S.M. Saleh-Koutahi, Evaluation of the effective dose during BNCT at TRR
thermal column epithermal facility, Appl. Radiat. Isotopes 110 (2016) 134.
[116] M.K. Marashi, Analysis of absorbed dose distribution in head phantom in boron neutron capture
therapy, Nucl. Instrum. Meth. A 440 (2000) 446.
[117] M.K. Marashi, N. Shadan-poor and A. Pazirandeh, Comparison of measured and calculated neutron
spectra for BNCT study, TȦm. Nucl. Soc. 65 (1992) 158.
[118] E. Sirai et al., Clinical Experience of BNCT for Brain Tumours at JAERI, in Progress in Neutron
Capture Therapy for Cancer, B.J. Allen, D.E. Moore and B.V. Harrington eds., Springer, Boston,
MA, U.S.A. (1992), pp. 569–576.
[119] H. Tanaka et al., Characteristics comparison between a cyclotron-based neutron source and
KUR-HWNIF for boron neutron capture therapy, Nucl. Instrum. Meth. B 267 (2009) 1970.
[120] O. Aizawa, Research on neutron beam design for BNCT at the Musashi reactor, in Neutron beam
design, development, and performance for neutron capture therapy, Springer (1990), pp. 109–124.
[121] I. Auterinen and S. Salmenhaara. FiR 1 reactor in service for boron neutron capture therapy (BNCT)
and isotope production, in proceedings of International Conference on Research Reactor
Utilization, Safety, Decommissioning, Fuel and Waste Management, 2003, pp. 123–130.
[122] F.M. Wagner and L. Koester, Fast neutrons for BNCT, Strahlentherapie und Onkologie 165 (1989)
115.
[123] G.W. Jackl, F.M. Wagner and A. Kraxenberger, Effect of Boron Neutron Capture on DNA
Fractionation, in Advances in Neutron Capture Therapy: proceedings of the Seventh International
Symposium on Neutron Capture Therapy for Cancer, B. Larsson et al. eds., Vol. II, Elsevier,
Amsterdam (1997), pp. 535–539.
[124] R. Tietze et al., Phantom Studies of Neutron Capture of Boron Containing Magnetic Nanoparticles,
Biomed. Eng./Biomed. Tech. (2013).
[125] M. Mitev, S. Belousov and K. Ilieva, Investigation on F/M material aspects of IRT-Sofia NCT
channel, Appl. Radiat. Isotopes 88 (2014) 180.
[126] H. Joensuu et al., Boron neutron capture therapy of brain tumors: clinical trials at the Finnish
facility using boronophenylalanine, Journal of Neuro-Oncology 62 (2003) 123.
[127] J. Capala et al., Boron neutron capture therapy for glioblastoma multiforme: clinical studies in
Sweden, Journal of Neuro-Oncology 62 (2003) 135.

– 25 –
[128] R. Henriksson et al., Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a phase II
study evaluating a prolonged high-dose of boronophenylalanine (BPA), Radiother. Oncol. 88 (2008)
183.
[129] N. Arkhangelsky et al., Current trends in and prospects for development of Russian research
reactors, in Proceedings of the third Eurasian conference on nuclear science and its application,
2004, pp. 19–30.
[130] V. Giusti, et al., Monte Carlo model of the Studsvik BNCT clinical beam: description and validation,
Med. Phys. 30 (2003) 3107.
[131] M. Capoulat, D. Minsky and A. Kreiner, Applicability of the 9 be (d, n) 10 b reaction to ab-bnct skin
and deep tumor treatment, Appl. Radiat. Isotopes 69 (2011) 1684.

2017 JINST 12 P05005

[132] C.N. Culbertson et al., In-phantom characterisation studies at the Birmingham
Accelerator-Generated epIthermal Neutron Source (BAGINS) BNCT facility, Appl. Radiat. Isotopes
61 (2004) 733.
[133] M. Capoulat and A. Kreiner, A 13 C (d, n)-based epithermal neutron source for Boron Neutron
Capture Therapy, Phys. Med. 33 (2017) 106.
[134] A. Kreiner et al., A Tandem-electrostatic-quadrupole for accelerator-based BNCT, Nucl. Instrum.
Meth. B 261 (2007) 751.
[135] K.-N. Leung, Compact Neutron Generator for BNCT, in Neutron Capture Therapy, Springer (2012),
pp. 55–67.
[136] J.M. Verbeke, Development of high-intensity DD and DT neutron sources and neutron filters for
medical and industrial applications, Lawrence Berkeley National Laboratory (2000).
[137] Y. Kasesaz and M. Karimi, A novel design of beam shaping assembly to use DT neutron generator
for BNCT, Appl. Radiat. Isotopes 118 (2016) 317.
[138] J. Ghassoun et al., On the 252 Cf primary and secondary gamma rays and epithermal neutron flux
for BNCT, Nucl. Instrum. Meth. B 263 (2007) 231.
[139] J. Ghassoun et al., Detailed dose distribution prediction of Cf-252 brachytherapy source with boron
loading dose enhancement, Appl. Radiat. Isotopes 68 (2010) 265.
[140] R. Martin, J. Knauer and P. Balo, Production, distribution and applications of californium-252
neutron sources, Appl. Radiat. Isotopes 53 (2000) 785.
[141] W.L. Araujo and T.P.R. de Campos, Design and investigations of a DD compact neutron generator
in head radiotherapy, in proceedings of International Nuclear Atlantic Conference, Recife, PE,
Brazil, November 24–29 2013.
[142] S.F. Brandão and T.P. Campos, Brain tumour and infiltrations dosimetry of boron neutron capture
therapy combined with 252Cf brachytherapy, Radiat. Prot. Dosim. (2011) 250.
[143] A. Brahme, Comprehensive Biomedical Physics, Elsevier Science (2014).
[144] R.L. Moss, Critical review, with an optimistic outlook, on Boron Neutron Capture Therapy (BNCT),
Appl. Radiat. Isotopes 88 (2014) 2.
[145] http://www.japantimes.co.jp/news/2016/04/06/national/science-health/japanese-researchers-to-test-
new-weapon-on-unbeatable-cancers/#.WO4WJvl97cs,
2016.
[146] M. Yoshioka et al., Development of an accelerator based BNCT facility in Ibaraki, in 15th
International congress on neutron capture therapy, Tsukuba, Japan, 2012, pp. 229–241.

– 26 –
[147] G.J. Storr et al., Design considerations for the proposed HIFAR thermal and epithermal neutron
capture therapy facilities, in Progress in neutron capture therapy for cancer, Springer (1992),
pp. 79–82.
[148] M. Papaspyrou and L.E. Feinendegen, Bioanalytical Investigations on Experimental BNCT with
Cold Neutrons at the Jülich Research Reactor FRJ-2, Status Report, in Progress in Neutron Capture
Therapy for Cancer, Springer (1992), pp. 289–291.
[149] F. Colomb, H. Carcreff and C. Morin, BNCT filter design studies at the CEA-Saclay ISIS research
reactor, Frontiers in Neutron Capture Therapy, Springer (2001), pp. 301–305.
[150] B.J. Allen, Neutron capture therapy research in Australia, Pigm. Cell Melanoma R. 2 (1989) 235.

2017 JINST 12 P05005

[151] http://www.jsnct.jp/e/about_nct/haikei.html.

– 27 –