I.

Project Research
Project 6

PR6Translational Research on BNCT for Clinical Application

M. Suzuki
Research Reactor Institute, Kyoto University

Background and Objective
Using Kyoto University Research Reactor (KUR),
patients with malignant tumors greater than 500 havebeen treated with boron neutron capture therapy(BNCT). Malignant brain tumors and head and neckcancers have been main malignancies treated with
BNCT. Our laboratory (Division of Particle Radiation Oncology) has investigated the possibilities for
new applications for BNCT. According to promising
results in pre-clinical study, we have already treatedsome patients with liver cancers with BNCT and carried out clinical study on phase I study on BNCT for
malignant pleural mesothelioma (MPM).
Promising clinical results of BNCT using the research reactor encouraged us to go to further stage of
BCNT using an accelerator-based (AB) BNCT system.
Co-operation of Kyoto University Research Reactor
Institute and Sumitomo Heavy Industry have developed AB BNCT system with compact cyclotron as anaccelerator. In 2012 and 2014, clinical studies on
BNCT for recurrent malignant brain tumors and headand neck tumors to get an approval as a medical device from the Pharmaceuticals and Medical Devices
Agency (PMDA), a Japanese regulatory agency. In atransition period from reactor-based (RB) BNCT into
AB-based BNCT, many research issues should be dissolved from impending and long-term viewpoints.
Main objectives of our project is to dissolve many
impending clinical issues to perform BNCT safely in
AB-BNCT system and to investigate many research
projects for many patients with cancer to be treatedwith AB-BNCT system.
Research Subjects
To advance RB-BNCT into AB-BNCT, a lot of researchers in various research fields such as clinicalradiation oncology, medical physics, pharmacology,
boron chemistry, and accelerator engineering areneeded to be involved in our research projects. In
this viewpoint, this research project consists of threeresearch subjects (RS) as follows,
RS1. Clinical studies on BNCT
RS2. Pre-clinical studies on physiological and pharmacological aspects of BNCT
RS3. Medical physics studies on BNCT.
Main Results
Six reports could be submitted although KUR has
been unavailable since May in 2014.

28P6

RS1. Clinical studies on BNCTNo BNCT was carried out since KUR has been unavailable in 2016.
RS2. Pre-clinical studies on physiological and pharmacological aspects of BNCT
Yanagie et al. reported two pre-clinical studies.
One was a preclinical study for evaluating
10
Boronophenylalanine (BPA) – entrapped water-in-oil
in water (WOW) emulsion. Another one was a study
for checking.
Fujimoto et al. investigated biodistribution of BPA
in metastatic bone of human cancer-bearing animalmodel.
RS3. Medical physics studies on BNCT
Taketa et al. developed a patient-position-error measuring system and tested the system.
Tanaka K et al. investigated suitable configuration of
the converter to combine with the imaging plate.
Sakurai et al. reported the development of the remote-changeable Bonner-sphere spectrometer.
Translational research on BNCT looking toward
accelerator-based BNCT era.
For three years when KUR has not worked, clinical
trials using AB-BNCT system has made steady progress. Therefore, more strategic translational research leading to clinical application in AB-BNCT
may be desired. These researches should be carriedout with attention to regulatory science. On the other
hand, more innovative or fundamental translational
researches are needed looking toward the future 10 or
20 years later.

PR6-1Preliminary formulation of 10Borono-phenylaranine entrapped WOW emulsion
for Neutron Capture Therapy to Hepatocellular Carcinoma

Hironobu Yanagie1,2,3, Mitsuteru Fujihara4, Ryuji
Mizumachi5, Yuji Murata5, Yuriko Sakurai1,3, Kikue
Mouri1,3, Atsuko Shinohara6,7, Takehisa Matsukawa7,
Ayano Kubota7, Yasuyuki Morishita8, Novriana Dewi2,
Masashi Yanagawa9, Sho Yui1,3,Kazuhito Yokoyama7,
Yasumasa Nonaka1, Hirotaka Sugiyama1, Yoshitaka
Furuya1, Yoshinori Sakurai10, Hiroki Tanaka10, Minoru
Suzuki10, Shinichiro Masunaga10, Koji Ono10, Minoru
Ono3,11, Jun Nakajima3,12, Masazumi Eriguchi13, andHiroyuki Takahashi2,31Dept of Innovative Cancer Therapeutics:Alpha particle &Immunotherapeutics, Meiji Pharmaceutical University,2
Dept of Nuclear Engineering & Management, Graduate
School of Engineering, The University of Tokyo,
3
Cooperative Unit of Medicine & Engineering, The
University of Tokyo Hospital, 4SPG Techno Ltd. Co., 5LSI
Medience Ltd Co, 6The Graduate School of Seisen
University, 7Jyuntendo University, 8Dept of Human &Molecular Pathology, Graduate School of Medicine, The
University of Tokyo, 9Veterinary Medical Center, Obihiro
University of Agriculture & Veterinary Medicine,10
Research Reactor Institute, Kyoto University, 11Dept ofCardiac Surgery, The University of Tokyo Hospital, 12Deptof Thoracic Surgery, The University of Tokyo Hospital,
13
Dept of Surgery, Shin-Yamanote Hospital
INTRODUCTION:
Water-in-oil-in-water(WOW)emulsion has been used as the carrier of anti-cancer agentsby modifying of IPSO on intra-arterial injections inclinical. Higashi et al prepared a long term inseparable
WOW for use in arterial injection therapy to treat patientswith hepatocellular carcinoma (HCC) by the double
emulsification technique [1]. We have previously
performed the preclinical BNCT study for VX-2 rabbit
tumour model using 10BSH entrapped WOW [2, 3], and we
also proceeded clinical BNCT study for HCC using thissystem [4].
In this study, we prepared 10BPA-entrapped WOW
emulsion and evaluated the boron encapsulating activity
by measuring the 10B concentrations of WOW using ICPAES.
EXPERIMENTS: We prepared the 10BPA-entrapped
WOW emulsion evaluate the properties by determining
boron concentrations of the WOW emulsion was using
ICP- AES at Juntendo University.

28P6-6RESULTS: 10BPA-entrapped WOW emulsion was
prepared by mixing 37.5mg of 10BPA, 83.3 mg of Fructose
in 8mL of WOW emulsion. 10B concentration of
precipitate of WOW emulsion, supernatant, and total
homogeneous mixing emulsion, were measured to be
255.5 g/mL, 93.8 g/mL, and 222.4±5.2 g/mL,
respectively.
In the case of 10BSH WOW emulsion, the original 10B
concentration was found to be 7000~13000 ppm, while inthe case of 10BPA, 10B concentration was 250 ppm. The 10B
concentration is very low, but 10BPA is incorporated into
the tumor cells by LAT-1 transporter. Therefore, it isexpected that we could evaluate whether the original
concentration is effective or not, in the VX-2 hepatic tumor
model.

Figure 1. Formulation of 10BPA WOW emulsion.
Left: Precipitate, Center: Supernatant, Right: Mix

The calculated osmotic pressure of each WOW emulsion
were as below:
Epirubicin WOW : 632 mOsm/L
10
BSH WOW (BSH 175mg+ D.W. 2.0mL): 909 mOsm/L
10
BPA WOW: 641 mOsm/L
The osmolality of 10BPA WOW was the same as
epirubicin entrapped WOW emulsion, so it will be easily
injected by catheter on the intra-hepatic administration.
We hope to perform toxicity examinations of WOW
emulsion to develop the more suitable WOW emulsion for
intra-arterial born delivery system.
REFERENCES:[1] S Higashi S et al., Cancer, 75(1995):1245–1254.
[2] S Mikado et al., Nucl. Instr. and Meth. A, 605 (2009):
171-174.
[3] H Yanagie et al., Appl Radiat Isot., 69(2011): 1854-7.
[4] H Yanagie et al., Appl Radiat Isot., 88(2014):32-7.

PR6-2Pre-BNCT Biodistribution of p-borono-L-phenylalanine in Metastatic Bone of
Human Breast Cancer-bearing Animal Model

T. Fujimoto1, T. Andoh2, Y. Sakurai3, M. Suzuki3 andH. Ichikawa2
1

Hyogo Cancer Center,
Department of Orthopaedic Surgery
2
Faculty of Pharmaceutical Sciences and Cooperative
Research Center of Life Sciences,
Kobe Gakuin University
3
Research Reactor Institute, Kyoto University
INTRODUCTION: Breast cancer, the most morbid malignancy in women, is frequently encountered in Japan.
Although most breast cancer is diagnosed at an earlystage, 20-30% of cases turn metastatic [1]. Furthermore,
about 70% of such cases metastasize to the bone [2].
When systematic pharmacotherapy is not effective insuch cases, the disease is difficult to control. Especiallyin the case of bone metastasis of lower extremities, there
is constant danger of pathological fracture that leads to alowering of the quality of life. Therefore, mainly surgery
with the use of intramedullary nails is carried out to prevent pathological fracture. Nonetheless, this entails not
only patient physiological distress, but also the enormous
treatment costs of surgery, rehabilitation and postoperative radiotherapy. Here, then, is where BNCT proffers the
only option, presently, for resolving these problems.
BNCT destroys, by one brief irradiation, individual tumor
cells without affecting surrounding normal tissue; therefore, for the management of bone metastasis with BNCT,
we evaluated the distribution of 10B in the bone of a
newly established human breast cancer-bearing animalmodel.
EXPERIMENTS: All animal experiments were carriedout according to the regulations of the Animal Care and
Use Committee.
(1) Tumor cell line: Cells of human breast cancer cell line
MDA-MB-231-luc were cultured in Leibovitz’s L-15
medium with fetal bovine serum in a 5% CO2 humidified
incubator at 37˚C.
(2) Producing bone metastasis in the human breast cancer-bearing animal model: Cells of MDA-MB-231-luc
suspended in Matrigel® were transplanted into the tibiaof the left hind leg of the nude mice. Eight weeks thereafter, micro-CT scans disclosed the formation of a tumor
in the left tibia. Histological examinations were then carried out by HE staining.
(3) Biodistribution of 10B in the bone-metastasis animalmodel: p-borono-L-phenylalanine (BPA)-Fr (24 mg
10B/kg) was intravenously injected into the tibia of thehuman breast cancer-bearing animal model and, at predetermined intervals, blood and normal bone samples
were collected immediately after the mice were killed.
The concentration of boron in the samples was thenmeasured by ICP-AES.

28P6-14RESULTS: Bone metastasis was successfully producedin the human breast cancer-bearing animal model. The
formation of a solid tumor mass in the left tibia was confirmed by macroscopic observation, micro-CT scans andmicroscopic analysis [Fig. 1]. Biodistribution of 10B: 1.5hours after the intravenous injection of BPA-Fr into thebone-metastasis animal model, tumor-specific andhigh-level 10B accumulation at a concentration of 22.7μg
10B/g of wet tumor tissue was identified in the bone tumor compared with normal bone [Fig. 2], with a tumor-to-normal bone ratio of 2.3. These results prognosticated that boron accumulates specifically in the bonetumor and that BNCT destroys tumor cells only at the siteof the bone metastasis, preventing bone fracture.

***[Fig.1] HE staining. Tumorigenesis within the tibial marrow cavity in the human breast cancer-bearing bone metastasis animal model. *: cortex, **: tumor.

[Fig.2] Biodistribution of 10B in the tumor and the normalbone of the human breast cancer-bearing animal model.
●: Tumor, ▲: Normal bone.
REFERENCES:[1] Metastatic behavior of breast cancer subtypes. H.
Kennecke et al. J Oncol, 28(2010) 3271-7.
[2] Clinical management of women with metastatic breast
cancer: a descriptive study according to age group. K.
Manders et al. BMC Cancer, 6(2006).

PR6-3

Nanoparticle-assisted Boron Neutron Capture Therapeutics: Design ofNovel Boron-containing Nanoparticle for ROS Scavenging Ability Improving
Therapeutic Efficiency with Low Adverse EffectZhenyu Gaoa,b, Yukichi Horiguchia, Kei Nakaib, Akira
Matsumurab,, Minoru Suzukic, Koji Onoc, Yukio Nagasakia, b, d*aGraduate School of Pure and Applied Sciences, University of Tsukuba,bGraduate School of Comprehensive Human Sciences,
University of TsukubacResearch Reactor Institute, Kyoto University,d
WPI-MANA, NIMS
INTRODUCTION: Boron neutron capture therapy(BNCT) has attracted much attention during recent decades. The success of BNCT is dependent on the borondelivery system to achieve high specific tumor accumulation, keeping low adverse effect. However, the low molecular weight boron compounds currently used in clinical trial of BNCT are excluded rapidly from the blood
circulation, which causes non-specific dispersing inwhole body. It is confirmed that high-dispersion stable
nanoparticle tends to accumulate in tumor environment
due to the leaky neovascularization and immature lymphatic systems, which is called enhanced permeability
and retention (EPR) effect1. Furthermore, during thetreatment process, large amount generated reactive oxygen species (ROS) will cause adverse effect such as inflammation. The objective of this study is to design anovel boron nano-delivery-system that enhance the therapeutic efficiency as well as suppress the adverse effect
EXPERIMENTS: The novel boron-containing nanoparticles (BNP) in this study was prepared by mixing a
newly synthesized boron-cluster-containing anionic block
copolymer (PEG-b-PMBSH) and a redox cationic block
copolymer (PEG-b-PMNT) via the ion complex in phosphate buffered saline (PBS) solution. The BNCT effectwas evaluated by using tumor bearing BALB/c mice
given BNP at dose of 15 and 5 mg 10B/kg body weight 72

28P6-15h before irradiation. Mice given boronophenylalanine(BPA)-fructose complex at dose of 40 mg 10B/kg bodyweight and PBS 2.5 h before irradiation were used as
positive and negative control. Tumor volume growing
was monitored. White blood cell levels were confirmed 3d after irradiation.
RESULTS: The size of the BNP was evaluated bydynamic light scattering (DLS), showing average
size of 35 nm and neutral surface. In the in vivo
BNCT effect evaluation study, the tumor volume in
PBS treated group grew up to 1.3 cm3 13 d after irradiation. In contrast, the growth of tumors was effectively suppressed in the BNP treated groups (average size was about 0.4 cm3, while the doses of 10B
were 15 and 5 mg/kg). The suppression of tumor
growth was also observed in the mice treated by
BPA with dose of 10B at 40 mg/kg, (average size
was 0.7 cm3). By much lower dose, 5 mg 10B/kg (5ppm boron in tumor tissue), BNP showed better
therapeutic effect compared with BPA. Furthermore,
we observed high white blood cell (WBC) level in
BPA treated group, indicating the inflammation was
occurred. However the WBC level in BNP treatedgroup (15 mg/kg) showed almost similar as the
non-tumor-bearing healthy mice, probably becauseof the ROS scavenging ability of BNP. These results
strongly indicates that this novel boron-containing
nanoparticle is a suitable potential candidate forhigh performance of BNCT improving the therapeutic efficiency with low adverse effect.
REFERENCES:[1] Y. Matsumura, H. Maeda, Cancer Research 46:
6387–92 (1986)

PR6-4

Toxicity Evaluation of 10BSH entrapped WOW emulsion on intra-arterial delivery
in Rabbits for Neutron Capture Therapy to Hepatocellular Carcinoma

Hironobu Yanagie1,2,3, Tsuyoshi Higuchi4, Mitsuteru
Fujihara5, Ryoji Mizumachi4, Yuji Murata4, Yuriko
Sakurai1,3, Kikue Mouri1,3, Yasuyuki Morishita6, Novriana
Dewi1, Masashi Yanagawa1,7, Yasumasa Nonaka1,
Hirotaka Sugiyama1, Yoshitaka Furuya1, Yoshinori
Sakurai8, Hiroki Tanaka8, Minoru Suzuki8, Shinichiro
Masunaga8, Koji Ono8, Minoru Ono3,9, Jun Nakajima3,10,Masazumi Eriguchi11, and Hiroyuki Takahashi2,31Dept of Innovative Cancer Therapeutics:Alpha particle &Immunotherapeutics, Meiji Pharmaceutical University,2
Dept of Nuclear Engineering & Management, Graduate
School of Engineering, The University of Tokyo,
3
Cooperative Unit of Medicine & Engineering, The
University of Tokyo Hospital, 4LSI Medience Ltd Co, 5SPG
Techno Ltd. Co., 6Dept of Human & Molecular Pathology,
Graduate School of Medicine, The University of Tokyo,
7
Veterinary Medical Center, Obihiro University ofAgriculture & Veterinary Medicine, 8Research Reactor
Institute, Kyoto University, 9Dept of Cardiac Surgery, The
University of Tokyo Hospital, 10Dept of Thoracic Surgery,
The University of Tokyo Hospital, 11Dept of Surgery, ShinYamanote Hospital
INTRODUCTION:
Water-in-oil-in-water(WOW)emulsion has been used as the carrier of anti-cancer agentsby modifying of IPSO on intra-arterial injections inclinical. Higashi et al prepared a long term inseparable
WOW by the double emulsification technique to be usedin arterial injection therapy to treat patients with
hepatocellular carcinoma (HCC) [1]. We previously
performed preclinical BNCT study for VX-2 rabbit tumour
model using 10BSH-entrapped WOW [2, 3, 4], and we also
proceeded clinical BNCT study for HCC using this system[5].
In this study, we prepared 10BSH-entrapped WOW, andevaluated the toxicity by checking survival conditions andbiochemical data after intra-hepatic injection of 10BSH
entrapped WOW emulsion in healthy rabbits.
10
EXPERIMENTS:
BSH-entrapped WOW wasadministrated with intra-arterial injections via proper
hepatic artery on healthy rabbits. As a part of the safety
evaluation of 10BSH-entrapped WOW emulsion, the test
article was dosed once by hepatic arterial administration to
3 male rabbits at 0.075 and 0.15 mL/kg to investigate its
toxicity. The control group was given lactose entrapped
WOW emulsion at 0.15 mL/kg.
The investigated items included clinical observation,measurement of body weights and food consumption,
blood chemistry, necropsy, and histopathology.

RESULTS: Body weight; no statistically significant
difference was noted in the 0.075 mL/kg group on Day 3
or 7 compared with the control group. However, decreased

28P6-17

body weights were noted in all animals in the control andtest article (0.075 and 0.15 mL/kg) groups on Day 3.
Blood chemistry; increases in the α1 globulin, α2globulin, β globulin, and total cholesterol, as well as
decreases in the albumin (g/dL and %) and A/G ratio werenoted in 1 male (No. 8) in the 0.15 mL/kg group on Day 7.
These were not considered to be attributed to BSH.
Surviving animals; there were no test article-relatedchanges in any of the BSH administration groups.
Adhesion was noted between the lobules of the liver in 1
male each of the 0.075 and 0.15 mL/kg groups andbetween the gallbladder and omental, duodenum, or liverin 2 males of the 0.075 mL/kg group and in 1 male of the0.15 mL/kg group. All of the changes were treatmentrelated; however, as they were also noted in the control
group or absent in the 0.15 mL/kg group, they were notconsidered to be attributed to BSH. There were nointergroup differences in their occurrence, so they were notconsidered to be attributed to BSH.
The minimum dose of WOW emulsion-containing BSH
is 3 mL in clinical practice. Based on the assumption that
it was given to an individual weighing 50 kg, the minimum
dose was calculated to be 0.06 mL/kg (3 mL/50 kg = 0.06
mL/kg). Accordingly, the lowest dose for hepatic artery
injection to rabbits was set at 0.075 mL/kg, which is higher
than the minimum dose (0.06 mL/kg), and the highest dose
at 0.15 mL/kg, which is twice the lowest dose (0.075
mL/kg) in this study.
We hope to refer these results of toxicity examinations
to the clinical studies of BNCT to hepatocellular
carcinoma with intra-arterial boron delivery using WOW
emulsion.
REFERENCES:[1] S Higashi S et al., Cancer, 75(1995):1245–1254.
[2] S Mikado et al., Nucl. Instr. and Meth. A, 605 (2009):
171-174.
[3] H Yanagie et al., Appl Radiat Isot., 69(2011): 1854-7.
[4] H Yanagie et al., Br J Radiol. (2017) [Epub ahead ofprint] doi:10.1259/bjr.20170004.
[5] H Yanagie et al., Appl Radiat Isot., 88(2014):32-7.

PR6-5

Exfoliation of Hexagonal Boron Nitride Nanosheet with Chlorin e6
and Application of the Composite to Cancer Photodynamic Therapy

Maruyama Kyouhei, Komatsu Naoki
Graduate School of Human and Environmental
Studies, Kyoto University
Recently, we directly fabricated the graphene-based
composite from graphite in the presence of chlorine6 (Ce6) by sonication in aqueous phase.1 The
composite (G/Ce6) was found to deliver the Ce6
into cancer cells and work as a photosensitizer forcancer photodynamic therapy (PDT). In this paper,
we used h-BN in place of graphite and realized
much higher Ce6 concentration in the composite ofh-BN/Ce6 than that of G/Ce6.
Aqueous dispersion of h-BN/Ce6 was preparedby use of commercially available h-BN and Ce6
under the same conditions as those in the preparation of G/Ce6. The formation of h-BN/Ce6 was
confirmed by the red shift of Q band in the absorption spectra and quenching of the fluorescence. In
comparison of these dispersions shown in Table 1,
the contents of Ce6 and the carrier were 10 and 20
times larger in h-BN/Ce6 than G/Ce6, respectively.
Since the size of h-BN is much smaller than that ofgraphite, it is concluded that h-BN was exfoliatedmuch more easily than graphite in the presence of
Ce6 in water. This is supported by the phenomenon
that the loading capacity of Ce6 on h-BN is half ofthat on graphene shown in Table 1.
The cytotoxicity of h-BN/Ce6 to HeLa cells was
confirmed under irradiation of 660 nm LED light asshown in Fig. 1. While Ce6 without carrier exhibited no cytotoxicity, viability of the cells significantly decreased to less than 20% at the Ce6 concentration of 0.4 mg/mL. This PDT effect by use ofh-BN/Ce6 is quite similar to that of G/Ce6, indicating no difference between h-BN and graphene as adrug carrier.

28P6-21

Table 1. Comparison of h-BN/Ce6 with G/Ce6.

h-BN/Ce6
G/Ce6

Ce6(µg/mL)
392
36

Carrier(µg/mL)
438
22

Loading(%)
80
160

Figure 1. Viability of HeLa cells in presenceof h-BN/Ce6 and Ce6 under light irradiation.

REFERENCE:[1] G. Liu, H. Qin, T. Amano, T. Murakami, N.
Komatsu, ACS Appl. Mater. Interfaces. 2015, 7,
23402.

PR6-6

Establishment of QA/QC Using Ionization Chamber andBonner Sphere in BNCT Field (III)Y. Sakurai, H. Ueda1, R. Uchida1, T. Takata, H. Tanaka, K.
Okazaki1, T. Kawamura1, K. Akita1,2 and M. Suzuki1
Research Reactor Institute, Kyoto University
Graduate School of Engineering, Kyoto University
2
Osaka Medical School
1

INTRODUCTION: Research and development
into several types of accelerator-based irradiation
systems for boron neutron capture therapy(BNCT) is underway [1,2]. In the near future,
BNCT using these newly developed irradiation
systems may be carried out at multiple facilities
across the world. Considering this situation, it isimportant that the estimations for dose quantityand quality are performed consistently among
several irradiation fields, and that the equivalency of BNCT is guaranteed, within and across
BNCT systems. Then, we are establishing thequality assurance and quality control (QA/QC)
system for BNCT irradiation field. As part of the
QA/QC system, we are developing estimation
method for neutron energy spectrum using Bonner sphere [3].

trometer was decided as follows: three sphereshells such as 13, 18 and 20 cm in diameter, andthree liquid moderators such as pure water,
0.028-wt% boron acid solution and 0.7-wt% boron
acid solution, as shown in Fig.2.
CONCLUSION: We have a plan to make theremote-changeable Bonner-sphere spectrometer,
based on the optimization result. Additionally, we
have a plan to perform the spectrometry experiments at Kyoto University Reactor (KUR), etc., inorder to confirm the efficacy of this spectrometer.

METHODS: Liquid such as pure water and/or
boric acid solution is used as the moderator. A
multi-layer concentric-sphere case with several
sphere shells is prepared. The moderator and its
diameter are changeable without entering theirradiation room, by the remote supply anddrainage of liquid moderator in the several layers.
For the detector, activation foils are remotelychanged, or online measurement is performed
using SOF (scintillator with optical fiber) detector
containing boron [4], etc.. The development of thisremote-changeable Bonner-sphere spectrometer isreported. The combination of the moderators forboron-10 (B-10) concentration and diameter was
optimized by our originally-developed method,“High Independence Selection (HIS)” [5]. The optimized combination was decided among 101
combinations; the combinations of ten B-10 concentrations and ten diameters, additionally thecase of manganin foil only without the moderator.

Fig. 2. Optimization for the structure of the remote-changeable Bonner-sphere spectrometer.

RESULTS: Figure 1 shows the response functions for the selected combinations. The optimized
combination was selected by HIS as follows:manganin foil only, 0.7-wt% boron acid solution of
13 cm in diameter, 0.7-wt% boron acid solution of
18 cm in diameter, 0-wt% boron acid solution(namely pure water) of 18 cm in diameter, and
0.028-wt% boron acid solution of 20 cm in diameter. Then, the optimized structure of the spec-

REFERENCES:[1] H. Tanaka et al., Nucl. Instr. Meth. B 267 (2009)
1970-1977.
[2] H. Kumada et al., Appl. Radiat. Isot. 88 (2014)211-215.
[3] H. Ueda et al., Appl. Radiat. Isot. 104 (2015) 25-28.
[4] M. Ishikawa et al., Radiat. Oncol. 11 (2016)
105(1-10).
[5] H. Ueda, Doctoral Thesis (2016).

28P6-22

Fig. 1. Response functions for the selected combinations.

PR6-7 Calculational Survey of Converter Configuration for Quality Assurance of BeamComponent Distribution at KUR Using Imaging Plate
K. Tanaka, Y. Sakurai1, T. Kajimoto, H. Tanaka1, T.
Takata1, M. Suzuki1 and S. Endo
Graduate School of Engineering, Hiroshima University
Research Reactor Institute, Kyoto University

1

INTRODUCTION: It is important to check the spatial
distributions of neutrons and gamma rays in the quality
assurance and quality control of boron neutron capture
therapy (BNCT). This study investigates the usage of theimaging plate (IP) for this purpose. The suitableconfigu-ration of the converter to combine with the IP
is investi-gated with calculational survey1.
METHODS: In order to separate the beamcomponents, the converters to enhance the beamcomponents is sup-posed to be used as follows: thermaland epithermal neu-trons will be enhanced by thesecondary particles from (n,α) reactions of the nuclides
such as 6Li, which reacts with low-energy neutrons;
fast neutrons enhanced by the recoiled protons fromthe hydrogen-rich material. For gamma rays, carbon
is used so that gamma rays are not depressed or
neutrons are not enhanced.
The converter configuration in order for the attemptedbeam component to dominate the IP signal intensity isinvestigated using PHITS 2.76. The geometry is shownin Fig. 1. The assumed irradiation fields are thestandard thermal neutron irradiation mode, mixed
neutron irradia-tion mode, and epithermal neutron
irradiation mode in KUR-HWNIF, with a power of 5
MW. The IP assumed is “BAS-TR” from Fuji Film
Corporation, Japan. The en-ergy deposition at the IPsensitive region is computed as a representative of the IP
signal.
a(mm)

neutron
gamma

5

a

b

5

c

IP #1

IP #2

CarbonMaterial #1

5

5

b
(mm)

neutron
gamma

5

a b

IP #1

IP #2

Carbon

c

5

d

e

5

IP #3

Polyethylene with LiF at 10 wt%

6

Li

1

ThermalEpithermal
Fast
Gamma

0.1

0.01

0.001

0

1

2

3

4

5

Polyethylene thickness in front of IP #2 (mm)Fig. 2 Energy deposition contribution in IP #2.
Table 1. Converter configuration selected. The attemptedbeam component is shown in parenthesis.
Converter ContribuMode
GeometryIP#matetialtion (%)
Thermal Fig. 1 (a) with 1
Carbon51.8 ()10-wt%(a, b, c) =99.3 (th)2
6Li-P.E.
(1, 1, 1 mm)
Mixed
Fig. 1 (b) with 1
Carbon54.9 ()(a, b, c + d, e)
10-wt%
93.2 (th)2
6Li-P.E.
=(1, 1, 5, 1
10-wt%
48.0 (epi)36Li-P.E.
mm)
EpiFig. 1 (b) with 1
Carbon69.4 ()thermal(a, b, c, d, e)
10-wt%
96.7 (epi)26Li-P.E.
=
P.E.
(1, 4, 1, 1, 1
3
without
30.9 (fast)mm)
LiF

Material #1 Material #2
5

Fig. 1 Calculation geometry.

28P6-23RESULTS and DISCUSSION: As an example of theresults, the energy deposition contribution in IP #2 in
10-wt% 6Li-P.E. for its thickness “b” varied, with a = c =d = e = 1 mm in Fig. 1 (b), is shown in Fig. 2 for standard
epithermal neutron irradiation mode. The epithermal neutron component is attempted in the IP #2. As “b” increased, the contribution of thermal neutrons decreased,
which resulted in 1.5% for the thickness at 4 mm. In addition, the contribution of epithermal neutrons slightly
increased from 94.4% to 96.7%. As a potential option, b= 4 mm was chosen.
As summary, the converter configuration selected andcontribution of attempted beam component to energy
deposition in IP is shown in Table 1.

REFERENCE:[1] K. Tanaka et al., Appl. Rad. Isot. 115 (2016) 212-220.

PR6-8 Initial Test Operation of Patient-Position-Error Measuring System for BNCT Irradiation
T. Takata, Y. Sakurai, H. Tanaka and M. Suzuki
Research Reactor Institute, Kyoto University

INTRODUCTION: In boron neutron capture therapy(BNCT) irradiations carried out at Kyoto University Research Reactor, sitting position has been applied in manycases, considering a flexibility of patient positioning andstructural restriction of an irradiation facility. In thosecases, the patient position is sometimes unstable, resulting in a displacement from an initial set-up position determined by a treatment planning process. The displacement and motion during an irradiation period cause uncertainty in estimation of delivered dose.
Aiming to improve the dose estimation accuracy, we
have been preparing a patient-position-error measuringsystem using a motion sensor [1]. The results of initialtest operation of the position measurement are described.
MATERIALS AND METHODS: A MEMS motion
sensor module (IMU-Z 2, ZMP Inc., Tokyo) consisting of
tri-axial accelerometer, gyroscope and magnetometer wasused to track a position and a rotation angle. The sensor
module (36×52×11 mm) and a battery box (36×62×15mm) were fixed to each other, and mounted on the top of
the head of a subject as shown in Fig. 1. The data was
acquired every 20 ms and registered in the PC by thewireless data transmission function built in the module.
The data registered was analyzed to estimate the position
and the rotation angle.
At first, the original measured data was smoothed byapplying a low-pass filter to remove the high-frequency
fluctuation component. Then, each vector data wastransformed from the sensor coordinate system to theroom coordinate system. After that, the phase of motion,that is, at rest or in motion was determined based on thechange rate in magnitude of the acceleration vector. The
position displacement was calculated by integrating theaccelerometer data twice with respect to time. Also, therotation angle was calculated by integrating gyroscope
data with respect to time in motion phase and by comparing the direction of gravitational acceleration andgeomagnetic field to the initial direction in resting phase.
RESULTS: Figure 2 shows an estimation result for therotation angle around each axis in the case of the headshaking motion from side to side, followed by the nodding motion. The periods of these motions were around 5
seconds. The room coordinate system were defined as theinitial sensor coordinate system as illustrated in Fig. 1.
The shaking is corresponding to the rotation around Z
axis and the nodding to the rotation around Y axis. It was
found that the rotation angle could be tracked correctlyby this system for the shaking motion during the elapsed
time of 5 to 20 seconds and for the nodding motion during the time of 20 to 30 seconds.
Figure 3 shows an estimation result for the position dis-

28P6-26

placement along each axis during the rotation motion
described above. The result showed no displacement
during the first 20 seconds and then showed large divergence after the beginning of nodding motion while theactual displacement was in a range of several centimeters.
It was found that the system could not work correctly inthe displacement estimation in this case.

Fig. 1. Mounting of the sensor system and the coordinate system definition.

Fig. 2. Estimated rotation angle during head shaking
and nodding motion.

Fig. 3. Estimated position displacement during headshaking and nodding motion.
REFERENCE:[1] T. Takata et al., KURRI Progress Report 2015 (2016)49.