PR 14

Translational Research on BNCT for Clinical Application

M. Suzuki

RS1. Clinical studies on BNCTTwo research groups reported case reports treatedwith BNCT using KUR. Miyatake et al. reported avery important case report from a clinical viewpoint of
new application of BNCT. In this report, radiation-induced osteosarcoma in the skull was successfully treated with BNCT. Kat et al, reported case reports of six patients with head and neck cancer.
Yanagie et al. reported the result of
18F-boronophenylalanine (BPA) – positron emission
tomography (PET) study which was taken by breast
cancer patient with right supraclavicular lymph nodemetastasis and treatment planning study.

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.

RS2. Pre-clinical studies on physiological and pharmacological aspects of BNCT
Nakamura et al. studied the effects of the countercations of boron clusters on liposome formation todevelop high boron content liposomes for BNCT byovercoming osmotic pressure limitations.
Gao et al. studied the therapeutic efficiency and suppression of the adverse effects of a novel boron-containing nanoparticles which were prepared bymixing a newly synthesized boron-cluster-containing
anionic block copolymer and a redox cationic bkicj
copolymer.
Fujimoto et al. studied the efficiency and potential of
BNCT for lung metastasis using the human clear cellsarcoma lung metastasis mouse model.
Tada et al. studied the feasibility of a boron-rich boron carbide (B4C) as a boron-including drug in BNCT
for oral cancer using xenograft nude cancer-baring
mice.
Yanagie et al. performed preclinical BNCT study for
VX-2 rabbit liver tumor model using borocaptate sodium (BSH) entrapped water-in-oil-in-water (WOW).

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.

RS3. Medical physics studies on BNCT

Hayashi et al. studied the NMR response of the standard
methacrylic-acid-based polymer gel (MAGAT) with andwithout boron and examined its availability to measure
the depth-dose responses in the irradiation of neutron
beams with different energy spectra from nuclear reactor.
Tanaka K et al. reported a calculational approach formeasurement of the beam components such as thermal,
epithermal, fast neutrons and gamma rays separately using twin imaging plate system.
Sakurai et al. studied the QA/QC in BNCT using ionaization chamber and Bonner sphere in BNCT irradiation
field.
Tanaka H et al. studied the prototype system of real-time boron concentration monitor.

Main Results
Unfortunately, KUR has been unavailable since May
in 2014. Many research subjects could not be performed.

採択課題番号 26P14（京大･原子炉）鈴木 実

BNCT 実用化に向けた橋渡し研究82

プロジェクトPR14-1 Boron Neutron Capture Therapy for Radiation-induced Osteosarcoma from the Skull
S. Miyatake, S. Kawabata, R. Hiramatsu, G. Futamura
T. Kuroiwa, Y. Sakurai1, H. Tanaka1, A. Maruhashi1,
M. Suzuki1, N. Kondo1, S. Masunaga1, Y. Kinashi1 andK. Ono1
Department of Neurosurgery, Osaka Medical College
Research Reactor Institute, Kyoto University

1

INTRODUCTION: From March 2014 to May 2014,
we applied boron neutron capture therapy (BNCT) for 11
lesions in KUR. The lesions were composed of 3 recurrent
glioblastomas, 2 recurrent anaplastic astrocytomas, 4high-grade meningiomas, 1 head and neck cancer and 1
recurrent osteosarcoma from the skull. We have alreadyreported the effectiveness of BNCT for malignant gliomas,
high-grade meningiomas and head and neck cancers,
however, that for osteosarcoma is extremely rare and noreport of BNCT was found for radiation-induced
osteosarcoma. Therefore we introduce here the successfultreatment of BNCT for radiation-induced osteosarcoma
from the skull.
Clinical Presentation:
A 54-year-old female was referred to our institute fortreatment by BNCT of a recurrent radiation-induced
osteosarcoma involving the left occipital bone. Ten years
earlier, she was diagnosed with cancer of the uterine bodyand underwent resection surgery. Two years after thatsurgery, she underwent chemotherapy and whole-brain
radiation therapy (WBRT, total 30 Gy with 10 fractions)
including the cerebellum for brain metastasis. Six years
after the WBRT, she was diagnosed with aradiation-induced osteosarcoma involving the left
occipital bone, and she underwent resection surgery andsuccessive chemotherapy using methotrexate. One year
after that surgery and chemotherapy, the subcutaneoustumor appeared again in the left occipital region andrapidly enlarged over a period of only 3 months (Figure 1
A). Magnetic resonance images (MRI) showed theepidural tumor invasion (Figure 2 A and A’). Eventually,
the patient could not walk because of acutely developing
cerebellar ataxia. This tumor was diagnosed as arecurrence of the radiation-induced osteosarcoma
We performed BNCT for this radiation-induced
osteosarcoma.
At one day after the BNCT, the patient’s gait
disturbance was aggravated. Computed tomography atthat time showed aggravation of peri-lesional edema(data not shown). Remarkably, the MRI taken 4 days
after the BNCT demonstrated the definitive shrinkage ofthe mass, but the left cerebellar edema was still there(Figure 2 B and B’). We then treated the edema withdehydrators and steroids. The symptoms gradually

improved.
At only 3 weeks after the BNCT, the patient was able towalk again stably without aid. The subcutaneous tumor
was reduced dramatically without radiation injury of thescalp, with time after BNCT, as shown in Figure 1 B and
C. The only adverse effect was hair loss inneutron-irradiation field, as shown in Figure 1 C. MRI
showed the further reduction of tumor and thedisappearance of the cerebellar edema (Figure 2 C andC’), 3 months after BNCT.
We experienced only a case of successful treatment of
BNCT for radiation-induced osteosacoma. Hopefullythese potential therapeutic effects will be applicable for
non-radiation-induced osteosarcomas which are generally
refractory for other treatment modalities.

Figure 1. Marked improvement of the subcutaneoustumor at 3 weeks after the application of BNCT.
A: Just prior to the BNCT; B: Seven days after the
BNCT; C: At 2 months after the BNCT,

Figure 2. MRI of the patient’s brain before and after the
BNCT.
A,A’:Just prior to BNCT
B,B’:4 days after BNCT
C,C’: 3 months after BNCT

採択課題番号26P14-4

熱外中性子を用いた悪性脳腫瘍に対する
プロジェクト非開頭中性子捕捉療法の臨床的研究（大医大・脳外）宮武伸一、黒岩敏彦、川端信司、平松 亮、二村 元、宮田とも、大村知久（京大原子炉）小野公二、増永慎一郎、鈴木 実、近藤夏子、田中浩基、櫻井良憲, 丸橋 晃
83

PR14-2

Clinical Studies on BNCT for 6 Cases of Head and Neck Cancer

I. Kato, T. Iwagami1, N. Yamamoto2, Y. Fujita3, M.
Ohmae4, M. Suzuki5, S. Masunaga5, H. Tanaka5, M.
Nakazawa, T. Sumi, A. S. Iwai, Maruhashi5, K. Ono5, Y.
Yurarate (OS) and 9-year OS were 42% and 31%, respectively.
(3)BNCT improved QOL, PS and survival periods.
(4)Survival periods after BNCT were 1-105 months. (5)Adverse events were brain necrosis, osteomyelitis andtransient mucositis and alopecia and so on.

Dept. of Oral &Max.fac. Surg. II, Grad. Sch. of Dent., Osaka Univ.
1

Dept. of Oral &Max.fac. Surg., Han-nan Hosp.

2

Dept. of Oral &Max.fac. Surg., Saiseikai-Senri Hosp,

3

Dept. of Oral &Max.fac.Surg., Higashiosaka General Hosp.

4

Oral &Max. fac. Surg., Rinku,General Med. Center5

Research Reactor Institute, Kyoto University

Case 4: A 56-year old man with SCC at the left marginof tongue (T2N0M0) had got interstitial radiation therapy(60Gy) at the Osaka University Hospital in July 2013,
with rejection against his doctor’s recommendation of thesurgery (tongue hemi-section). About 6 months after theinterstitial radiotherapy, he had developed the left lymph
node metastasis at upper neck region (level II). However,
he had again rejected to the surgery of radical neck dissection against his doctor. During his rejection of thesurgery, the lymph node had rapidly grown more than
7cm in diameter, involving carotid vein and artery. He
had referred to our department in March 2014.
FBPA-PET study resulted that T/B ratio=4.2. The left
upper neck lymph node had treated with BNCT in May,
2014. About 3 month later, the huge lymph node hadcompletely disappeared under the CT scan. Then
6-month after BNCT, he had complaint of dyspnea. He
had seen his general practitioner and his doctor advised
him to see specialist. He had found the left lung lesions
which were seemed to be distant metastasis under the CT
scan. He had got chemotherapy for treatment of lunglesions at a hospital in his home town.

INTRODUCTION: We had first reported that six patients with head and neck cancer (HNC) had been treatedwith BNCT [1]. We also report long term (more than
5-year) clinical outcomes of our 26 patients with recurrent HNC treated with BNCT [2]. We summarized here
the latest 6 patients with HNC who had treated with
BNCT at KUR in last year in Table 1.
PURPOSES: The purpose of this study was to estimate
safety and effectiveness of BNCT for patients with advanced/ recurrent HNC for which there were no othertreatment options.
RESULTS: We also report here the latest clinical outcomes of 37 patients with recurrent HNC
All cases are advanced such as 18 (49%) out of 37 patients had developed regional lymph node metastases.
Distant metastases were developed in 10 cases (27%)
during treatment. (1) Regression rates were CR:19cases(51%), PR: 14 cases (38%), PD: 3cases (8%), NE (notevaluated):1case (3%). Response rate was 89%. (2) Mean
Survival time was 26.3months. 4-year overall survival

REFERENCES:[1] I. Kato, et al., Appl. Radiat. Isot., 61 (2004)
1069-1073.
[2] R. Barth, et al., Radiat. Oncol., 7 (2012) 146-166

Table 1. Treatment Summary of 6 Cases
Case
No.

Pt‘s Initial(Age)

Clinical Diag.
(Histopathol. Diag.)1

K・M(28)Rec.of Lt-ZK (SCC)

２

K・M(63)

Rt-op.OKK、RND, Lt-LN meta

３

A・H(51)

Rt-op.ZK,RND,BNCT, lung meta

4

I・T(56)

Post RT of Lt-ZK, Lt-LN meta

５

S・K(69)Rt-OGK(SCC)after Proton T.

S・M(69)Rec.of Rt-op.UGK, RND,

6

10B-conc.
Blood(ppm)
1st 16.7
2nd 15.0
33.3
23
22
26.5
20.0

T-max of thermal neutron (D)

T/B
ratio

Total-RBE-Dose Eq (Gy-Eq)

History of RT:
(Gy)

2.9

Fluence(E+11n/cm -2)
1.5(Left-P)
1.4(Left-A)

T-Peak Gy-Eq

Skin/Mucosa

45（2.1 ㎝）

T-deepest
Gy-E
12
15
21（5.8 ㎝）

48

23
20

3.9

2.8

50

2.8

1.8

63

26（1.6 ㎝）

8.8(6 ㎝)

4.2

2.52

60(interstitial)

50

2.1

3.79

70(Proton T.)

30

2.0

3.36

60

34

18
12
13

Irradiationtime(min.)(Dec, 2014)% Reduction (Period)
Prognosis (Survival)

5.7/11

1st 66 min.
2nd 46 min.

PR・Alive(6M)

4.4/1352

PD（2M）Alive(（9M）

2.6spine80

PR(2M),DOC(8M)7.9/1270

CR(7M),Lung meta

8.3/12

44

12/14

63

PD, DOC(3M)
CR, Lung meta,DOC(6M)

採択課題番号26 P14-5 頭頸部悪性腫瘍におけるホウ素中性子捕捉療法の臨床的研究 プロジェクト（阪大 2 口外）加藤 逸郎、岩井 聡一、墨 哲郎、中澤 光博、由良 義明（阪大工）村田 勲（慶大）岡本 正人（長崎大）梅田 博昭、柳本 惣市（りんくう医療セ）大前 政利（東大阪総合）
千足 浩久（市立池田）大西 徹郎（田中クリニック）田中 善（山口大）上山 吉哉、内田 堅一郎（京大炉）田中 浩基、鈴木 実、櫻井 良憲、増永 慎一郎、丸橋 晃、小野 公二
84

PR14-3

Boron Uptake in Tumour of Local Recurrenced Breast Cancer by 18F-BPA
Positron Emission Tomograpy for Application to Boron Neutron Capture Therapy
Atomic Research Ractor 4. This simulation was performed optimizing modification to detect the minimum
thermal neutron fluence.

Yanagie H1,2,3, Furuya Y1,4, Taniike K5, Kumada H6,
NakamuraT7, Horiguchi H7, Maruyama S8, Hatae R8,
Suzuki M9, Ono K9, Ono M3,10, Nakajima J3,11, Eriguchi
M1,8, and Takahashi H2,3

RESULTS: The blood boron concentration (ppm) andtumour/normal tissue ratio are estimated to 24, 2.26, respectively. Skin RBE dose is ristricted to 10 Gy-Eq, themaximum tumour RBE dose, minimum tumour RBE
dose, and mean tumour RBE dose are 38.5, 19.9, and30.6 Gy-Eq, respectively, in 40 minutes irradiation(Figure 2). In this study, we showed the possibility toapply BNCT to local recurrenced advanced breast cancer
with the estimation of boron accumulation using
18F-BPA Positron Emission Tomograpy.

1

Department of Innovative Cancer Therapeutics: Alphaparticle & Immunotherapeutics, Meiji Pharmaceutical
University, 2Department of Nuclear Engineering &Management, Graduate School of Engineering, The University of Tokyo, 3Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, 4Departmentof Surgery, Satukidai Hospital, 5Department of Radiology,
Nishijin Hospital, 6Department of Physics, Tsukuba University, 7Japan Atomic Research Institute, 8Department ofSurgery, Shin-Yamate Hospital, 9Research Reactor Institute, Kyoto University, 10Department of Cardiac Surgery,
The University of Tokyo Hospital, 11Department of Thoracic Surgery, The University of Tokyo Hospital
INTRODUCTION: Boron neutron capture therapy(BNCT) is a targeted radiation approach, because tumour cells can be selectively irradiated according to theaccumulation of boron compounds. The cytotoxic effectof BNCT is due to the nuclear reaction between 10B andthermal neutrons. The resulting lithium ions andα-particles have high linear energy transfer and produce
significant biological effects. Their short range in tissue(5 – 9 μm) restricts radiation damage to cells containing
boron atoms at the time of neutron irradiation. If sufficient boron compound can be targeted accurate to thetumour, BNCT can be applied to locally recurrenced gastrointestinal cancers, and breast cancers.
Recently, positron emission tomograpy(PET) is developed for primary detection and metastasis of cancers. 18F
labeled borono-phenylalanine (BPA)-PET are applyed toevaluate the accumulation of boron atoms to tumours andthe actibity of cancer cells in the fields of BNCT.

Figure 1. 18F-BPA PET image of rt cervical LN
metastasis.

CASE REPORT: We had experienced the 18F-BPA PET
for the case of breast cancer patient who had metastased
to right supraclaviclar lymph node. The patient who had
been performed modified radical mastectomy with lymph
node dissection (Patey’ s method) and adjuvant chemotherapies, had been occurred right cervical LN metastasis
after 3 years. The high accumulating images of metastased to right supraclaviclar lymph node was acquired by
18F-BPA PET. The tumour / blood ratio was 2.26 (Figure1). There was no other active images in the body.

Figure 2. Image of Patient View from frontal side
REFERENCES:[1] Y Imahori et al., Clin Cancer Res. 4(1998 )1833-41.
[2] Y Imahori et al., Clin Cancer Res. 4(1998 )1825-32.
[3] H Yanagie et al., Applied Radiation & Isotopes,
67(2009) S63-66.

EXPERIMENTS: In this case of advanced breast
cancer, we performed the feasibility estimation of 3D
construction of tumour according to the PET-CT imaging
of a patient with epithermal neutron mode at Japan

採択課題番号26P14-8 中性子捕捉療法の一般外科領域難治性癌への展開に向けた臨床的研究 プロジェクト（明薬大）柳衛宏宣、野中泰政（結核予防会新山手病院）江里口正純、小山和行、大野烈士、丸山正二、波多江 亮（宏仁会メディカルシティ東部病院）東 秀史、瀬口浩司（京大・原子炉）小野公二、増永慎一郎、
鈴木 実、櫻井良憲

85PR14-4

High Boron-Accumulated Liposomes as Efficient Boron Carriers for
Neutron Capture Therapy

H. Nakamura1, S. Tachikawa2, S. Kikuchi1, K. Ono3 and
M. Suzuki3

sionelectronmicroscopy
analysisof
spd-BSH-encapsulating
liposomes
andNa2BSH-encapsulating liposomes was also carried out
with Cryo-TEM (Fig. 2). It is notable that the liposomes
interacted with each other in the case of
Na2BSH-encapsulating liposomes, whereas the liposomes
dispersed in solution without interacting with each otherin the case of spd-BSH-encapsulating liposomes.

1

Chemical Resources Laboratory, Tokyo Institute ofTechnology
2
Faculty of Science, Gakushuin University
3
Research Reactor Institute, Kyoto University
INTRODUCTION: Boron neutron capture therapy(BNCT) has been attracting growing interest as one of theminimally invasive cancer therapies. The accelerator-based BNCT is now undergoing phase I clinical study
for the treatment of brain tumor and head and neck cancer patients using L-BPA in Japan. We previously developed Na2BSH-encapsulating 10% distearoyl boron
lipid (DSBL) liposomes that have high boron content
with excellent boron delivery efficacy to tumors.[1] In
this report, we studied the effects of the counter cationsof boron clusters on liposome formation to develop highboron content liposomes for BNCT by overcoming osmotic pressure limitations.

Fig. 2. TEM images of Na2BSH-encapsulating liposomes(left) and spd-BSH-encapsulating liposomes (right). Scale bar represents 200 nm.
Fig. 3 shows the survival curve of tumor-bearing mice
after thermal neutron irradiation. Thermal neutron irradiation enhanced mouse survival and all mice exposed tothermal neutron irradiation died within 78 days. Remarkable antitumor effect was observed in the micetreated with spd-[10BSH]-encapsulating liposomes at thedose of 30 mg [10B]/kg; 100% of the mice survived up to
100 days after the thermal neutron irradiation.[2]EXPERIMENTS: An aqueous solution of various ammonium chloride salts (1,4-diaminobutane, spermidine,and spermine) of closo-dodecaborates Na2[B12H12],Na2[B12H11OH] and Na[B12H11NH3] in addition to
Na2BSH (Fig. 1), were prepared by adding sodium closo-dodecaborates to a mixture of each amine and aqueous
1N HCl solution. Liposomes encapsulated with theseammonium closo-dodecaborates were prepared from
DSPC, cholesterol and DSPE-PEG (1:1:0.11, molar ratio)by the reverse-phase evaporation method. B/P (boron
concentration / phosphorus concentration) ratio was calculated from data obtained by the simultaneous measurement of boron and phosphorus concentrations by inductively coupled plasma atomic emission spectroscopy(ICP-AES, HORIBA, Japan).
2 Na+

SH

2-

2 Na+

H

2-

2 Na+

OH

2-

Na+

NH3

1"

Survival"rate

0.8"

Na2[B12H12]Na2[B12H11OH]

0.4"
0.2"
0"

-

0"

10" 20" 30" 40" 50" 60" 70" 80" 90" 100"Days"a9er"irradia;on"(d)

Fig. 3. Survival curve of tumor-bearing mice after thermal neutron irradiation. The irradiation was performed 36
h after injection of closo-dodecaborates (▬ , spd-BSH: 30
mg[10B]/kg; ◆ , spd-BSH: 15 mg[10B]/kg; ◇ ,spd-10B12H11NH3: 15 mg[10B]/kg) for 50 min (1.3-2.2 ×
1012 neutrons/cm2). ×, Cold control; ●, Hot control.

=B= BH
Na2BSH

0.6"

Na[B12H11NH3]

Fig. 1. Structures of closo-dodecaborates used for encapsulation in liposomes.
RESULTS:
Various ammonium salts of closo-dodecaborates were prepared and examined their encapsulation into liposomes. Interestingly, the B/P ratio
dramatically increased to 3.4 when spermidinium (spd)cation was employed. In addition, liposome yield wasmarkedly increased to 98% and final boron concentrationof the liposome solution reached 13,867 ppm. Transmis-

REFERENCES:[1] H. Koganei, et al., Bioconjugate Chem. 24 (2013)
124-132.
[2] S. Tachikawa, et al., Chem. Commun. 50, (2014)
12325-12328.

採択課題番号 26P14-16 中性子捕捉療法のための新規ホウ素薬剤の開発	
 プロジェクト	 （東工大・資源研）中村浩之、菊地俊介（学習院大・理）立川将士（京大・原子炉）小野公二、鈴
木実	
 

86

PR14-5

Boron Carbide Particle as a Boron Compound for BNCT in vivo

S Tada1, T Iwagami2, Y Ishikawa3, N Koshizaki4, H
Tanaka5, S Masunaga5, Y Sakurai5, I Kato1, K Ono5, M
Suzuki5, Y Yura1
Osaka University Graduate School of Dentistry
Hannan Municipal Hospital3
National Institute of Advanced Industrial Science andTechnology
4
Graduate School of Engineering, Hokkaido University
5
Research Reactor Institute, Kyoto University
1

2

Figure 1: Nude mice carrying SAS tumors received 50µl of 250 ppm B4C solution intratumorally. Ten
minutes later, tumors were exposed to thermal neutrons. The experimental groups were as follows: untreated control, neutron only, and B4C-mediated
BNCT. n=5

INTRODUCTION: We determined whether a boron-richboron carbide (B4C) nanoparticle could be used for
BNCT for oral squamous cell carcinoma (SCC) xenografts in nude mice.
EXPERIMENTS: B4C nanoparticles were obtained by
the laser fragmentation of boron particles in ethyl acetate
and dissolved in PBS. To generate tumors, SAS cells derived from oral SCC were inoculated subcutaneously into
the back of the leg of female Balb/c nude mice. Fifty microliters of B4C solution containing 12.5µg B4C particles
was infiltrated into tumors. 10B concentrations in thesetissues were measured by prompt gamma-ray spectrometry at the Kyoto University Research Reactor (KUR).
After injection of B4C solution, tumors were exposed tothermal neutrons. Control tumors were left untreated.
Experimental groups included untreated control, neutron
only, and B4C-mediated BNCT groups. Neutron irradiation was delivered via a neutron beam at the KUR.
RESULTS: Injecting B4C particles into the oral SCC
xenografts of nude mice increased the concentration of
10B in the tumors, but not in the kidney, liver, or spleen.
Ten minutes after injection of B4C particles the 10B
concentration was 18.57 ppm in the tumor. SAS tumor-bearing animals received an intratumoral injection of
B4C solution followed by neutron irradiation. No significant differences were observed in body weight among
these groups during the experimental period (Figure 1).
In control animals, tumors continued to grow and were5867 mm3 42 days after the start of the experiment.
When tumors were subjected to B4C-mediated BNCT,
tumor volume decreased from 7 days after neutron irradiation. A significant difference was observed between the
B4C -mediated BNCT and neutron only groups 42 days
after BNCT (P<0.01) (Figure 2).
CONCLUSION: These results indicate that B4C particles
can be used locally as a boron compound in BNCT for
oral SCC in vivo.

採択課題番号 26P14-1

Figure 2: Nude mice carrying SAS tumors weretreated as described in Figure 1. After BNCT, tumor
size was measured and tumor volume was determined. *P< 0.01 significantly different from neutrons only. n=5References[1] Ishikawa Y, Shimizu Y, Sasaki T, Koshizaki N(2007) Boron carbide spherical particles encapsulated ingraphite prepared by pulsed laser irradiation of boron inliquid medium. Applied Physics Letters 91:161110.
[2] Ishikawa Y, Sasaki T, Koshizaki N (2010) Submicron-sized boron carbide particles encapsulated in turbostratic graphite prepared by laser fragmentation in liquid medium. J Nanosci Nanotechnol 10:5467-5470.
[3] Yamamoto N, Iwagami T, Kato I, Masunaga S, Sakurai Y, et al. (2013) Sonoporation as an enhancing
method for boron neutron capture therapy for squamouscell carcinomas. Radiat Oncol 8:280.

ᝏᛶ⭘⒆࡟࠾ࡅࡿ࣍࢘⣲୰ᛶᏊᤕᤊ⒪ἲ࡟㛵ࡍࡿᇶ♏◊✲ プロジェクト（阪大・歯）多田晋也、加藤逸郎、由良義明、（阪南・歯）岩上隆紀、（京大・原子炉）田中浩基、
櫻井良憲、増永慎一郎、鈴木実、丸橋晃、小野公二
87PR14-6 Boron Neutron Capture Therapy Selectively Destroys Human Clear Cell Sarcoma (CCS)
Metastasis to Lung in CCS-bearing Animal Model
T. Fujimoto1, T. Andoh2, Y. Sakurai3, K. Ono3,
H. Ichikawa2 and M. Suzuki3

paraffin-embedded, and HE stained according to standard
protocols for histological examination.

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

RESULTS: The irradiation doses (Gy) absorbed by the
CCS-bearing mice were 5.2 (Group A, BNCT), 0.7(Group B, Hot control) and 0.9 (Group D, γ-ray). In thethree control groups, no significant anti-tumor effect wasobserved; the tumor mass simply increased
time-dependently. By contrast, the volume of the tumor
mass in the BNCT groups decreased with time [Fig. 1].

INTRODUCTION: Sarcoma metastasis to the lung isalmost the final status for the treatment of sarcoma, andpalliative therapy is recommended for reducing severe
patient symptoms. Since neither chemotherapy nor radiation therapy is effective for most sarcomas, new therapeutic strategies are required. Clear cell sarcoma (CCS)of tendons and aponeuroses is one such with poor prognosis [1]. We have, however, demonstrated the effectiveness of boron neutron capture therapy (BNCT) for tumors
in the limbs of the human CCS-bearing nude mousemodel with the use of p-boronophenylalanine (BPA) [2,3]. Here, therefore, we first created a new model of sarcoma metastasizing to the lung in the human
CCS-bearing animal model, and then evaluated the efficacy and potential of BNCT after measuring the distribution of BPA in the lung.

CONCLUSION: BNCT selectively destroyed CCS cells
in the lung of the human CCS-bearing animal model byirradiating the whole lung, without significant complications.

EXPERIMENTS: (1) Creating the lung metastasis
model of human CCS-bearing animal model: All animal
experiments were carried out according to the regulationsof the Animal Care and Use Committee. Lung metastasis
in the human CCS-bearing animal model was created bytransplanting cells of CCS cell line (MP-CCS-SY [4])suspended in Matrigel® into the parenchyma of the left
lung of nude mice. After 8 weeks, tumor formation in thelung was confirmed by micro CT scans, and the tumor
mass was measured through CT image analysis.
(2) In BNCT trials, the animals were divided into fourgroups of 4 each, and, under anesthesia, BPA-Fr (24 mg
10B/kg) was intravenously administered to the BNCT
group (A) and to the Cold control group (C), and saline to
the Hot control group (B) on day 0. Groups A and B werethen irradiated two times with a thermal neutron beam
(1MW) to the whole lung at KURRI, once anteriorly
between 60 and 80 minutes and once posteriorly between
100 minutes and 120 minutes. The γ-ray group (D) was
irradiated with cobalt-60 γ-ray at a dose of 0.3 Gy/min.
On day 21, the tumor mass was resected from eachmouse under anesthesia, routinely formalin-fixed,

採択課題番号 26P14-19[Fig.1] BNCT for the lung metastasis model of
CCS-bearing animal model. a: Before neutron irradiation.
A well-defined solid tumor mass about 2 mm in diameter
was detected in the left lung. b, c and d: three weeks after
the neutron irradiation. b: Group A. BNCT. Tumor mass
shrank and was hardly discernible. c: Group B. Hot control. Neutron irradiation without administration of BPA.
Tumor mass was almost 3 mm in diameter. d: Group C.
Cold control. Without neutron irradiation. Tumor mass
was almost 4 mm in diameter. e: Group D. Three weeks
after theγ-ray irradiation. Tumor mass was almost 4 mm
in diameter. Bar = 2.5 mm.
REFERENCES:[1]F.M. Enzinger, Cancer, 18(1965) 1163-1174.
[2]T. Fujimoto et al., Appl. Radiat. Isot. 73(2013) 96-100.
[3]T. Andoh et al., Appl. Radiat. Isot.
69(2011)1721-1724.
[4]H. Moritake et al., Cancer Genet. Cytogenet.,
135(2002) 48-56

悪性末梢性神経鞘腫および明細胞肉腫

プロジェクトに対するホウ素中性子捕捉療法の検討（京大・原子炉）鈴木実、櫻井良憲、小野公二（兵庫県立がんセンター・整形外科）藤本卓也（神戸学院大・薬）安藤 徹、市川 秀喜

88PR14-7

Nanoparticle-assisted boron neutron capture therapeutics:
Design of novel 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*

BNCT effect was evaluated by using tumor bearing
BALB/c mice given BNP at dose of 15 and 5 mg
10
B/kg body weight 72 h before irradiation. Micegiven boronophenylalanine (BPA)-fructose complex at dose of 40 mg 10B/kg body weight and PBS
2.5 h before irradiation were used as positive andnegative control. Tumor volume growing was monitored. White blood cell levels were confirmed 3 dafter irradiation.

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, NIMSRESULTS: The size of the BNP was evaluated bydynamic light scattering (DLS), showing average
size of 35 nm and neural 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 of10
B 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

INTRODUCTION: Boron neutron capture therapy(BNCT) has attracted much attention during recent
decades. The success of BNCT is dependent on theboron delivery 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, whichcauses non-specific dispersing in whole body. It is
confirmed that high-dispersion stable nanoparticle
tends to accumulate in tumor environment due tothe leaky neovascularization and immature lymphatic systems, which is called enhanced permeability and retention (EPR) effect1. Furthermore, during
the treatment process, large amount generated reactive oxygen species (ROS) will cause adverse effectsuch as inflammation. The objective of this study is
to design a novel boron nano-delivery-system thatenhance the therapeutic efficiency as well as suppress the adverse effect.
EXPERIMENTS: The novel boron-containing
nanoparticles (BNP) in this study was prepared bymixinga
newly
synthesizedboron-cluster-containing anionic block copolymer(PEG-b-PMBSH) and a redox cationic block copolymer (PEG-b-PMNT) via the ion complex inphosphate buffered saline (PBS) solution. The

REFERENCES:[1] Y. Matsumura, H. Maeda, Cancer Research 46:
6387–92 (1986)

	 採択課題番号 P14-20	
 高い腫瘍選択性を有するボロン化合物ナノ粒子の創製とプロジェクト
中性子捕捉療法への展開	
 （筑波大院・数理）高	  振宇、堀口諭吉、長崎幸夫（筑波大院・人間）中井	
  啓、松村	  明（京大・原子炉）鈴木	
  実、小野公二	 89

PR14-8 Evaluation of Component in WOW Emulsion as Intra-arterial Boron Delivery Carrier 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, Yasuyuki
Morishita8, Masashi Yanagawa9, Syushi Higashi10, Ichiro
Ikushima11, Kouji Seguchi10, Sho Yui1,3,Yoshinori Sakurai12, Hiroki Tanaka12, Minoru Suzuki12, Shinichiro
Masunaga12, Kazuyuki Oyama13, Takayuki Nakagawa14,
Ryohei Nishimura14, Koji Ono12, Minoru Ono3,15, Jun
Nakajima3,16, Masazumi Eriguchi13, and Hiroyuki
Takahashi2,3patic artery (10BSH : 75 mg/kg rabbit) on VX-2 rabbit
hepatic tumour models. One and three days after arterial
injections, the boron concentrations of the tumor nodules
and normal liver tissues were determinated by ICP- Mass
Spectroscopy of Jyuntendo University.
RESULTS: VX-2-bearing rabbits (n = 3) were given
intra-arterial injection with 2 ml of 10BSH WOW emulsion consist with surfactant HCO40, or PGCR. We
prepared 10BSH entrapped WOW.
The mean 10B10
concentration prepared in BSH-WOW was 10000 ppm
in this experiment. The size of WOW was controlled to
70 μm. The 10B concentration in VX-2 tumour was 170.8
ppm, 58.3 ppm by WOW with HCO40 after day1, day3
inta-arterial injection, respectively. The 10B concentration of tumour was 186.0ppm, 40.4ppm by WOW with
PGCR after day1, day3 same injection, respectively. 10B
concentration in normal liver tissue / blood were 8.0 /0.3 ppm in HCO40 group, and 15.1 / 0.1 ppm in PGCR
group at day 3, respectively in the same procedures ofWOW. We also perform Oil-O Red staining to detect thelipid components in WOW. We had showed the stainingof cytoplasms in the tumours 3 day after itra-arterial injections(Figure 1) . These means that the WOW accumulated selectively to the tumours by intra-arterial injections.

1

Department of Innovative Cancer Therapeutics:Alphaparticle & Immunotherapeutics, Meiji Pharmaceutical
University, 2Department of Nuclear Engineering &Management, Graduate School of Engineering, The
University of Tokyo, 3Cooperative Unit of Medicine &Engineering, The University of Tokyo Hospital, 4SPG
Techno Ltd. Co., 5Department of Pharmacology,
Kumamoto Institute Branch, LSI Medience Ltd Co,
6
Department of Humanities, The Graduate School of
Seisen University, 7Department of Hygines, Faculty of
Medicine, Jyuntendo University, 8Department of Human& Molecular Pathology, Graduate School of Medicine,
The University of Tokyo, 9Department of Small Animal
Surgery, Veterinary Medical Center, Obihiro University ofAgriculture & Veterinary Medicine, 10Department ofSurgery, Ko-jin Kai Medical City East Hospital,
11
Department of Radiology, Miyakonojyo Metropolitan
Hospital, 12Department of Veterinary Surgery, The
University of Tokyo Veterinary Hospital, 13Research
Reactor Institute, Kyoto University, 14Department ofSurgery, Shin-Yamanote Hospital, 15Department of
Cardiac Surgery, The University of Tokyo Hospital,
16
Department of Thoracic Surgery, The University ofTokyo Hospital.

Day 1

Day3

NormalLiver

INTRODUCTION: We has been used water-in-oil-in-water emulsion (WOW) as the carrier of anti-cancer agents by modifying of IPSO on intra-arterial
injections in clinical. Higashi et al prepared a long term
inseparable, WOW for use in arterial injection therapy totreat patients with HCC [1]. We performed preclinical
BNCT study for VX-2 rabbit tumour model using 10BSH
entrapped WOW [2, 3]. In order to improve the WOW for
application to BNCT, we prepared 10BSH entrapped
WOW in verifying the component of surfactant, andevaluated the boron delivery activity to measure the 10B
concentrations of organs in VX-2 hepatic tumour modelon time course after intra-arterial injection.

TumourFigure1: IPSO component in WOW was accumulated inthe VX-2 tumour by intra-arterial injection of 10BSH
entrapped WOW with HCO40 surfactant by Soft X ray
radiography.
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., Biomedicine & Pharmacotherapy,
submitted.

EXPERIMENTS: 10BSH entrapped WOW were administrated with intra-arterial injections via proper he-

採択課題番号26P14-22

中性子捕捉療法の一般外科領域難治性癌への応用に向けたプロジェクト
DDSの基礎的研究（明薬大）柳衛宏宣、伊藤智子（東大）Novriana Dewi、柳川将志、櫻井由里子、毛利きくえ（大阪市大）長崎 健、吉川亮平、櫻本昌士（京大原子炉）小野公二、鈴木 実、櫻井良憲、田中浩基

90PR14-9

Establishment of QA/QC Using Ionization Chamber andBonner Sphere in BNCT Field

H. Ueda, Y. Sakurai, T. Takata, H. Tanaka, R. Uchida, T.
Kawamura, N. Fujimoto, M. Suzuki
Research Reactor Institute, Kyoto University
INTRODUCTION: After the restart of the operation of
Kyoto University Reactor (KUR) in May 2010, 235 clinical studies of boron neutron capture therapy (BNCT)
have already been carried out as of May 2015 [1]. Also,
the BNCT clinical trial using Cyclotron-based BNCT
Epi-thermal Neutron Source (C-BENS) started in November 2012 [2]. In the while, the research and development into several types of accelerator-based irradiation
systems are underway by several research groups in theworld at present time. With this situation in mind, it isimportant that the physical and biological estimations fordose quantity and quality are performed consistently
among several irradiation fields, and that the equivalencyof BNCT is guaranteed, even across BNCT systems. The
aim of this research is the establishment of quality assurance and quality control (QA/QC) using ionizationchamber and Bonner sphere in BNCT irradiation field. In
2014, the improvement of the energy resolution in
epi-thermal neutron region was studied for the Bonner
sphere using boric acid solution moderator.

Fig. 1. Unfolding results in the case that the activation detector displacement of 3 mm occurs on the
10-cm diameter Bonner sphere and the error is notconsidered in the unfolding procedure.

METHODS: The Bonner sphere in this research consistsof a spherical neutron moderator shell and activation foils
placed in the sphere center as thermal neutron detector.
The boric acid solution of 10B 0.14wt% was used as themoderator material. Manganin (55Mn) and gold (197Au)
were used as activation foil material. The specific saturated activities per neutron flux for each energy groupwere calculated as the response function of Bonner
spheres. The calculations were performed for the spherediameter of 10, 15 and 20 cm, using the MCNP-5 radiation transport code [3]. The calculated activities were
unfolded into the estimated spectrum by UMG unfolding
package [4]. The influence of the uncertainty for themoderator concentration and the detector placement tothe spectrum estimation, were investigated. The spectrum
estimation was performed for the epi-thermal neutron
irradiation mode in Heavy Water Neutron Irradiation Facility (HWNIF) of KUR was studied.

Fig. 2. Unfolding results in the same case as Fig. 1
except the error is considered.
REFERENCES:[1] Y. Sakurai et al., Nucl. Instr. Meth. A 453 (2000)
569-596.
[2] H. Tanaka et al., Nucl. Instr. Meth. B 267 (2009)
1970-1977.
[3] X-5 Monte Carlo Team, LA-UR-03-1987 (2003).
[4] M. Reginatto, The ’Few-Channel’ Unfolding Programs in the UMG Package (Physikalisch-Technische
Bundesanstalt) (2004).

RESULTS: Figure 1 shows the results in the case that theactivation detector displacement of 3 mm occurs on the
10-cm diameter of Bonner sphere. The error was notconsidered in the unfolding procedure. Figure 2 shows
the unfolding results in the same condition as Fig. 1, except the error was considered. In Fig. 1, the neutron energy spectrum is estimated wrongly. In Fig. 2, the neutronenergy spectrum is estimated more adequately, but theerrors of the estimated spectrum become larger.

採択課題番号 26P14-26

ＢＮＣＴ用照射場における電離箱およびプロジェクトボナーボールを用いたＱＡ／ＱＣの確立（京大・原子炉）櫻井良憲、田中浩基、鈴木 実、藤本 望、上田治明、内田良平、川村徳寛
91PR14-10

Study on the Real-time dose Monitor System Using Prompt Gamma Rays
for Boron Neutron Capture Therapy

H. Tanaka, Y. Sakurai, N. fujimoto, T. Takata, S.
Masunaga, K. Ono, A. Maruhashi, and M. Suzuki

direction, the patient was set between 0 cm and 60cm.
The background of gamma rays were produced by the1
H(n,)2D reactions with the energy of 2.22MeV, the annihilation gamma rays of 0.511 MeV, and the decay
gamma rays of 41Ar. The gamma rays at the near the collimator center are almost of 2.22 MeV produced in thehuman body. For the lateral direction, the level of gamma
rays were rapidly reduced. On the other hand, at the distance from the center of 60 cm, the dose rate of beam
direction was two times higher than that of lateral direction. This was caused by the 41Ar or annihilation gamma
rays produced by the reaction between thermal neutron
and the component of irradiation bed. Therefore, for the
beam direction, the level of gamma rays was slowly decreased. If the real-time boron concentration monitor isset at the BNCT field, it is recommended to set at thebehind of collimator for the lateral direction.

Research Reactor Institute, Kyoto University
INTRODUCTION: Over 500 clinical studies of boron
neutron capture therapy (BNCT) have been performed
using Kyoto University Research Reactor (KUR). The
information of neutron flux and boron concentration during the irradiation is needed for the determination of irradiation time. The boron concentration is determined by
the prompt gamma rays from the blood sample using
thermal neutron guide tube at KUR. On the other hand,neutron flux is measured by the activation material,
which is irradiated by the treatment beam and picked up
after 10 minutes from the irradiation start. However, theinformation of boron concentration and neutron flux is
not be able to be obtained during the irradiation. In orderto determine precise dose information, it is important todetect real-time boron concentration and neutron flux.
Recently, the real-time neutron flux monitor have beendeveloped using the combination of tiny scintillator andoptical fiber. The real-time boron concentration monitor
have been studied using SPECT system for BNCT[1].
However, the actual level system have not realized, because the background of gamma rays at the BNCT irradiation field is quite high. The aims of this study are toclarify the gamma rays dose level at the BNCT irradiation field and the development of the prototype system ofreal-time boron concentration monitor. The measured
gamma rays dose during BNCT clinical studies is shownin this report.

Fig. 1. Schematic layout of BNCT irradiation fieldof KUR and the setting position of TLDs.

EXPERIMENTS: The BeO thermoluminescence dosimeters (TLDs) were used for the measurement of
gamma rays dose. BeO powder was enclosed in quarts
tube to reduce the neutron sensitivity. The TLDs were set
at the position that was assumed to set the real-time boron concentration monitor. Figure 1 shows the schematiclayout of irradiation field and the TLDs setting positions.
The TLDs were set from the center of collimator for thelateral and beam direction with the 20 cm interval. The
height of TLDs setting position was the 60 cm, corresponding to beam center height. The irradiation was performed for head and neck tumor. The irradiation time was
63 minutes. After the irradiation, TLDs were processedby the TLD reader and the gamma rays dose were derived
with the correction.

Fig. 2. The relationship between gamma rays dose
rate and the distance from the center of collimator.
REFERENCES:[1] T. Kobayashi et al., Medical Physics, 27, 2124(2000)

RESULTS: Figure 2 shows the gamma rays dose rate
distribution for lateral and beam direction. For the beam

採択課題番号 26P14-27 BNCT のための即発ガンマ線によるリアルタイム
線量評価システムに関する研究

プロジェクト（京大・原子炉）田中浩基、櫻井良憲、藤本望、高田卓志、増永慎一郎、小野公二、丸橋晃、鈴木実

92PR14-11 Quality Assurance of Irradiation Field for BNCT Using Twin Imaging Plate System
Kenichi Tanaka, Yoshinori Sakurai1, Tsuyoshi Kajimoto,
Hiroki Tanaka1, Takushi Takata1, Jun Takada2,
Minoru Suzuki1, Satoru Endo

the beam component to the total of the energy deposition.
Here, the configuration “A-B” means that the energy
deposition for the converter ‘B’ is subtracted from thatfor ‘B’. “50% B – 10% B” or “Epoxy –Graphite” is notsuitable to use since some of the components have negative value in contribution.
In using two IPs, “50% B – Epoxy or Graphite” is potential for nepi, while 20 % of the energy deposition is byunintended component, nth. On the other hand, combining“10% B – Epoxy or Graphite” and “10% B – 1% B”, i.e.
using triple IP in Epoxy converters at 0, 1, 10 wt % of 10B,
will work in estimating nth and nepi.

Graduate School of Engineering, Hiroshima University
Research Reactor Institute, Kyoto University
2
Center of Medical Education, Sapporo Medical University
1

INTRODUCTION: Measurement of the spatial distributions of neutrons and gamma rays is one of the potentialand essential options for the quality assurance and quality
control for boron neutron capture therapy (BNCT). It is
desirable to measure the beam components such as thermal, epithermal, fast neutrons (nth, nepi, nf) and gamma
rays (), separately. This study investigates using the twin
imaging plate (IP) system for this purpose. A calculational approach is reported here.

ThermalEpithermal
Fast
Gamma

1 mm thick Epoxy
Energy deposition(MeV/sec/mA)

1000000
100000CALCULATIONS: The twin IP system consists of theconverters to enhance the components, and IPs. The principle is: thermal and epithermal neutrons will be enhanced with the secondary particles of the 10B(n,)7Li
reaction in the epoxy resin doped with boron, fast neutrons with the recoiled protons from the epoxy resin,
gamma rays with Graphite, then enhanced components
will be detected with the IPs. By comparing two IPs, intensity of a beam component is to be estimated[1,2].
The configuration of the converters was surveyed using
Monte Carlo calculations with PHITS 2.52[3]. The irradiation field assumed was that by the 7Li(p,n) reaction by
2.5 MeV protons moderated with 20 cm thick D2O. The
calculation geometry consisted of an IP (Fujifilm corporation, BAS-TR) and a converter. The IP in dimension of
20 X 20 mm was assumed to be covered with 1 mm thickconverter[1] in every direction of the IP. Each beam component was separately impinged on the converter as aparallel beam perpendicular to the IP. The epoxy resin
assumed was its compound with B4C, where boron wasenriched 10B with abundance of 100 %. The 10B concentration in epoxy resin (wt%) was varied in calculations.

10000
1000
100
0.01

10

0.1

1

10

100

B concentration in Epoxy (% )Fig. 1. Energy deposition for Epoxy at varied 10B concentration.
1 mm thick Epoxy

Ratio to total

1

ThermalEpithermal
Fast
Gamma

0.1
0.01
0.001
0.01

10

0.1

1

10

100

B concentration in Epoxy (% )Fig. 2. Beam component contribution to energy deposition.
Table 1 Energy deposition ratio (%) to total for subtraction among two IPs in converters.
Contribution (%)
Configuration
nth
nepi
nf

10% B –
50
50
00Epoxy or Graphite
50% B –
2080
00Epoxy or Graphite
10% B – 1% B
28
72
0
0
50% B – 10% B
-100
200
0
0
Epoxy – Graphite-14-5-43 162“x %B” specifies the epoxy resin with B4C at x wt% of
10
B to total weight of the converter.

RESULTS: The energy deposition in IP is shown in
Fig. 1. Those for Graphite converter is 425, 546, 1570,
and 13300 MeV/sec/mA for nth, nepi, nf, and , respectively. The contribution of each beam component to totalof the energy deposition is shown in Fig. 2. Again, thosefor Graphite is 0.3, 0.4, 1.2, 98.1 % for nth, nepi, nf, and 
In usage in twin IP system, it is desirable that only one
beam component has different energy deposition among
two IPs while other components have identical values,
respectively. In this viewpoint, Epoxy converters with 1
to 50 wt% of 10B will be potential options for detecting
nth, nepi.
Consequently, potential combinations of twin IPs arelisted in table 1. The values shown are the contribution of

REFERENCES:[1] K. Tanaka et al., Appl. Rad. Isot. 88 (2014) 143-146.
[2] K. Tanaka et al., Appl. Rad. Isot. 69 (2011) 1885-1887.
[3] H. Iwase et al., Jour. Nucl. Sci. Technol. 39 (2002)
1142-1151.

採択課題番号 26P14-28
プロジェクトイメージングプレートを用いた BNCT 照射場ビーム成分ごとの 2 次元分布品質保証（広島大・工）田中憲一、遠藤暁（京大・原子炉）櫻井良憲、田中浩基、（札幌医大）高田純
93

PR14-12

Development and Evalution of 3D Polymer Gel Dosimeter for the
Measurement of dose Distribution in BNCTS. Hayashi, Y. Sakurai1, M. Suzuki1, M. Narabayashi1and N. Fujimoto1

tron beams of the different energy spectrum modes. In
the thermal neutron mode, both profiles of the gels withand without boron show monotonically decreasing withdepth after the peak near the surface. It seems that thedecrease for the gels with boron corresponds to decreasing of thermal neutron in tissue and the peak shifts tonear the surface significantly due to the reaction withboron. In the epi-thermal and fast neutron mode, broad
peaks are observed at deeper position, around from 20 to
25 mm of depth. It is suggested that the R2 profile for the
gel with boron corresponds to the distribution of thethermal neutron due to the moderation of epi-thermal
neutron. But for the gels without boron, it seems that thedecreases correspond to decreasing of gamma ray. As
same as the profiles in thermal mode, the peak shift due
to boron was also observed. The depth profiles of themixed mode (not shown) were similar to that of thermal
neutron. It is suggested that the contributions of
epi-thermal and fast neutrons are small compared to thatof thermal neutron. These results indicate both MAGAT
gel dosimeters with and without boron have the effective
sensitivity on the thermal neutron rather than on fastneutron.

Department of Clinical Radiology, Hiroshima International University
1
Research Reactor Institute, Kyoto University

INTRODUCTION:
Polymer gel dosimeters havebeen investigated for the three-dimensional (3D) dose
measurement of the complex conformal dose distributions in the clinical applications [1]. These devices utilize
radiation-induced polymerization reactions of vinyl
monomer in the gel to preserve information about theradiation dose. The 3D absorbed dose distribution is deduced from the polymer distribution measured by imaging modalities, such as MRI. The applications to neutron
irradiation have been investigated, and the potential as a
3D dosimeter has been suggested [1].
In this work, the NMR response of the standard
methacrylic-acid-based polymer gel (MAGAT) with andwithout boron was examined its availability to measure
the depth-dose responses in the irradiation of neutron
beams with different energy spectra from nuclear reactor.

(These results were presented at 8th International
Conference on 3D Radiation Dosimetry : IC3DDose2014 in Ystad, Sweden. [2])EXPERIMENTS: Boric acid, B(OH)3, containing 10Bof 20% naturally was added into the standard gel The
concentration in the gel is the same order (approximately
50 ppm) as the clinical use. The resulting solution was
subdivided by pouring into quartz tall beakers (65 mm
diameter and 135 mm length, 400 mL).
The neutron irradiations were performed using Heavy
Water Neutron Irradiation Facility (HWNIF) of Kyoto
University Research Reactor (KUR, power of 1 MW) .
The samples were irradiated from the bottom direction
through the axis with the field size of almost 50 cm diameter in air at room temperature. The three different
modes (thermal neutron rich, epi-thermal and fast neutron rich, and the mixed modes) of neutron beams madeby heavy water spectrum shifter and cadmium thermal-neutron filters were applied to each sample.
MRI measurements were performed using a 1.5 T
scanner (Siemens). A multiple spin-echo sequence wasapplied and the transverse relaxation rate (R2 = 1/T2) was
estimated.

MAGAT/B(OH) 3 (Thermal)
MAGAT/B(OH) 3 (Epi−thermal and fast)
MAGAT (Thermal)
MAGAT (Epi−thermal and fast)3∆R 2 (/s)

2

1

0

0

20

40

80
60
Depth (mm)

100

120

Figure 1 The depth from phantom surface vs. ΔR2[=R2 – R2,bg ] responses in different energy spectra.
REFERENCES:[1]
C. Baldock et al., Phys. Med. Biol. 55 (2010)
R1–63
[2]
S. Hayashi et al., J. Phys.: Conf. Ser. 573 (2015)
012074(4pp)

RESULTS: Figure 1 shows the depth-R2 profiles obtained from our polymer gel dosimeters exposed to neu-

採択課題番号 26P14-29	
 BNCT における吸収線量分布測定のためのプロジェクトポリマーゲル 3 次元線量計の開発と特性評価	 （広国大・保健医療）林慎一郎（京大・原子炉）櫻井良憲、鈴木実、楢林正流、藤本望	
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