CO1-1

Analysis of Heavy Metal Elements in Chinese Medicine and Herbs

E. Furuta, N. Iwasaki, R.Okumura1 and Y. Iinuma1

structure of the 2 Chinese medicines of total 7 samples,
which were produced in China and Japan.

Ochanomizu University

RESULTS and DISCUSSION:

1

Jiedu Pian, 3 samples produced in China, were contained

Research Reactor Institute, Kyoto University

All of Niuhuangfrom 2.2 to 8.6% of As and from 1.2 to 74 ppm of Hg.
The main mineral was realgar by XRD, and the chemical
INTRODUCTION:

Chinese medicines and herbs

structure of As was sulphide; As4S4. We could not findwere analyzed in a previous experiment at KUR. At thatthe products except for Chinese one. On the other hand,results, toxic elements of As and Hg were contained withamong 4 samples, 2 of Liushen Wan were produced inhigh concentrations in 2 Chinese medicine; Niuhuang

China, and contained approx. 7% of As and 7.5% of Hg.

Jiedu Pian and Liushen Wan. However, when they are

Also, among 2 Japanese Liushen Wan, one for child wassulphide, they were not absorbed into the body. So, thecontained approx. 1% of As and 30ppm of Hg, and one

chemical structures are very important. Furthermore, low

for adult was contained approx. 550 ppm of As and 1.2

concentrations of Hg were contained in many Chinese

ppm of Hg. The main minerals of these 2 Chinese

medicines and herbs. However, Chinese medicines andLiushen Wan were realgar and cinnabar by XRD; As4S4

herbs produced in Japan contained these toxic elements

and HgS. On the other hand, the main minerals of these 2

rarely. The previous experiment raised mainly 3 queries;

Japanese Liushen Wan were gold and calcite by XRD; Au

1. Do the same named medicines contain same toxic

and CaCO3. So, the same named medicines neverelements with same level concentrations? 2. Whatcontained same toxic elements with same levelchemical structures were the As and Hg? 3. Do notconcentrations. Because the chemical structures were

Chinese medicines and herbs produced in Japan containsulphide, they are not absorbed into a body, but justtoxic elements? The purpose of this study was to clear

given a shock for the body. So, toxicity of the elements

these issues.

was no problems. Additionally, some minerals in Chinese

EXPERIMENTS:

Additional samples used in thismedicines tended to contain other toxic elements like Co,

study were 30. (The total sample number was 149.) They

Cr and Sb by INAA. Furthermore, almost all herbs

were grinded into powders with an agate mortar andcontained low level concentration of Hg. It was

enclosed each in a double polyethylene bag byconsidered the sources of Hg of low concentrations were

measuring their weight. The standard samples used werenot

JA-2 and JR-2 of rock standard, and 50 ppm of As, Hg,

contamination in the air.

Sb, Co and Cr of atomic absorption reagents (Wako)

Conclusion:

were used applying to 5 filter papers (Advantec 5A). The

medicine contained high concentration of toxic elements

samples and the standards were irradiated 1MW × 30

and many herbs contained low concentration of Hg;

min at KUR. After cooling among 5 to 10 days, thehowever, it was considered their chemical structures

gamma-rays of medium and long half life radionuclides

were not dangerous. At the same time, the safety images

were measured. Also, a XRD was used to study chemicalof Chinese medicines and herbs were not correct.

mineralsbutgrounddust

It was clarified that some Chinese

採択課題番号 26001
漢方薬、薬草に含まれる重金属元素の分析（お茶の水女子大学）古田悦子 （京大・原子炉）奥村良、飯沼勇人

96

contamination or

通常採択

Status Report 2014 for B–3 Beam Port of KUR
been refined on the basis of a cubic CaF2-type structurewith a = 4.288(1) Å, using X-ray diffraction with Cu Kα
radiation (see Fig. 2(b)). As shown in Fig. 2(a), we succeeded to observe several Bragg reflections for the(Ti0.31Cr0.33V0.36)D1.7 on the B–3 beam port; which could
be indexed on the basis of λ = 1 Å. Note that the Braggreflections correspond to the D–D correlations because of
the null alloy.
Furthermore, the data acquisition group of the neutronscience division of KEK (KEK–KENS DAQ group) has
used the B–3 beam port to assess their new 6Li-glass neutron detector system, LiTA12. The LiTA12 system consists of a 6Li-glass neutron detector with a multianodephoto multiplier tube (MA–PMT), an amplifier, and ananalog-to-digital converter (ADC) board. The B–3 beam
port has a wide space around the sample position; therefore we can easily install any other system like the
LiTA12 system.

K. Mori, H. Yoshino, Y. Iinuma, T. Fukunaga, Y. Kawabata, S. Sato1, H. Hiraka1, K. Iwase2, Y. Yamaguchi3, K.
Enjuji4, K. Furuta4, and T. Kasai4
Research Reactor Institute, Kyoto University (KURRI)
1
High Energy Accelerator Research Organization (KEK)2
Department of Materials and Engineering, Ibaraki University
3
Institute for Materials Research, Tohoku University
4
Graduate School of Engineering, Kyoto University
INTRODUCTION: The B–3 beam port of Kyoto University Research Reactor (KUR) had long been used as afour-circle single-crystal neutron diffractometer (4CND).
For the last decade, however, the 4CND was so old thatits research activity on neutron science was quite low.
Therefore, the 4CND needed to be replaced and a newneutron diffractometer has been required at the B–3 beam
port. Also, the new neutron diffractometer (Compact
multipurpose neutron diffractometer) is critical for the
structural investigations of energy storage materials suchas hydrogen absorbing alloys and rechargeable lithium-ion batteries. The neutron (powder) diffraction is a
powerful tool to determine the positions of light elements(e.g., hydrogen and lithium) in solids. Here, we report thecurrent status of the B-3 beam port of KUR and the preliminary neutron diffraction experiments using a hydrogen absorbing alloy.

(a)

INSTRUMENT: The compact multipurpose neutron
diffractometer is now being installed on the B–3 beam
port. The neutron wavelength (λ), which is monochromatized by the (220) plane of a Cu single crystal, is 1 Å. To
cover the detector area (6 º ≤ 2θ ≤ 150 º), 24 3He tube
detectors (1/2 inch in diameter) have been prepared. The
distances from the monochromator to the sample andfrom the sample to the detector will be 1.9 m and 1.2 m,
respectively. Fig. 1(a) shows the goniometer for thecompact multipurpose neutron diffractometer; we performed an operation check. A detector bank including the
24 3He tube detectors will be placed on an arm of thegoniometer. In addition, the new beam shutter was installed at the B-3 beam port, as shown in Fig. 1(b).

(b)

Fig. 1. Current status of the B-3 beam port of KUR: (a)new goniometer for the CMND and (b) new beam shutter
installed at the B-3 beam port.

(b)
4000

110

1000

400

2000

Observed data
Calculated data

200

3000

220

420

Intensity / counts

500

400

220

1000

Observed data
Calculated data

222

Intensity / counts

1500

311
222

(a)
200

CO1-2

70

90

0
FCC

0

Laves

PRELIMINARY EXPERIMENTS: The preliminary
neutron diffraction experiments were performed using thehydrogen absorbing alloy, (Ti0.31Cr0.33V0.36)D1.7, where D
is the deuterium. It is worth noting that Ti0.31Cr0.33V0.36 isa null alloy for neutron scattering due to its atomic compositions (i.e., bc[Ti0.31Cr0.33V0.36] = 0; bc[Ti] = –3.370 fm,
bc[Cr] = 3.635 fm, and bc[V] = –0.443 fm), where bc isthe coherent scattering length. The crystal structure has

20

30

40

50

2θ / °

60

70

40

50

60

80

100

2θ / °

Fig. 2. Neutron and X-ray diffraction data for a hydrogenstorage alloy, (Ti0.31Cr0.33V0.36)D1.7, collected at (a) theB-3 beam port of KUR and (b) a X-ray diffractometerwith Cu Kα radiation.

	 採択課題番号 26007	
  材料研究および中性子検出器開発を目的とした	
  	
  	
  	
  	
  	
  	
  	
  	
  通常採択
共同通常	
  	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 	
 小型多目的中性子回折装置の建設	
 （京大・原子炉）森一広、吉野泰史、飯沼勇人、福永俊晴、川端祐司（高エネ研）佐藤節夫、平賀晴弘（茨城大・工）岩瀬謙二（東北大・金研）山口泰男（京大院・工）延壽寺啓吾、古田幸三、笠
井拓矢	
 
97

CO1-3Synthesis of Metal Nanoparticles under the Gamma-ray Irradiation Field(JEOL JEM-2000FX). Samples for TEM observations
were made by putting a drop of colloidal solutions on acarbon film with a Mo mesh and dried them in a vacuum.

F.Hori, T.Hori, A.Tohkai, H.Nakanishi, A.Iwase,
M.Sakamoto2
Dept. of Mater. Sci., Osaka Prefecture University
1
Research Reactor Institute, Kyoto University

RESULTS:
Figure 1 shows the UV/vis absorption spectra for
aqueous solutions before and after gamma-ray irradiation.
It appears only one absorption peak around 570 nm,
which shows pure Cu nanopartcles production, after
gamma-ray irradiation. This is quite different from theresult that of adding of DEG [1]. This result clearlyshows that only pure Cu nanoparticles were generated
and no oxidation takes place during gamma-ray
irradiation. This is because ethylene glycol act as the
scavenger of oxidation radicals from H2O by gamma-ray
irradiation radiolysis. TEM observation shows thatgenerated particles are monodispersive spherical shapeand its average diameter is about 17 nm (fig. 2).

INTRODUCTION: It is known that metallic
nanoparticles have some specific properties, which are
not appear in bulk materials such as catalytic activities,
magnetic properties and so on. Also the character of them
depends on its size, shape, structure, chemicalcomposition and so on. For instance, it is known that Au
nanoparticles exhibit the surface plasmon resonances(SPRs) in specific wavelength at about 520 nm. They
have many possibilities to applied for various industrial
fields. Generally, many kinds of metal nanoparticles
commercially are synthesized by using chemical reaction
method. On the other hands, it has been reported thatspecific feature of metallic nanoparticles can besynthesized under energetic irradiation fields, such as
ultrasonic, electron, gamma-ray, plasma and so on. Using
these irradiation reduction methods, it is possible tofabricate the unexpected structured nanoparticles. So far,
we have successfully synthesized Cu nanoparticles,
which is not easy to reduce in aqueous solution bychemical reaction, by using gamma-ray irradiation
reduction method [1]. However, many of them are not
only pure Cu but also copper oxides. In this study, we
have tried to fabricate pure Cu nanoparticles by adding of
ethylene glycol instead of diethylene glycol.

Fig. 1 UV/vis absorption spectra of aqueous solutions

including Cu-ions
irradiation.

EXPERIMENTS: Aqueous solutions with a given
concentration of copper complex ((CH3COO)2Cu·H2O)
with an additive of of sodium dodecyl sulfate (SDS) andethylene glycol (EG). The solution was argon gas purged
and sealed into polystyrene vessels. They were irradiatedat about 300 K with 1.17 and 1.33 MeV gamma-rays
from 60Co radio active source at gamma irradiation
facility in KURRI, Kyoto University. The total dose was
fixed to 23.4 kGy with dose rate of 15.6 kGy/h. UV–vis
absorption spectra were measured by using Shimadzu
UV-2550 spectrophotometer in the wavelength range in
300-800 nm and the shapes and the structures for all
colloidal products were observed by conventional TEM

beforeandafter

gamma-ray

Fig. 2 TEM image of synthesized Cu nanoparticles by

gamma-ray irradiation reduction.
References[1] T.Hori, K.Nagata, A.Iwase and F.Hori, Jpn. J. Appl. Phys.
53(5), 2014	 採択課題番号 26010	
  	
  ガンマ線照射還元を利用した貴金属ナノ微粒子の創成（阪府大・工）堀史説、堀達朗、東海旭宏、仲西穂高、岩瀬彰宏	
 	
 (京大・原子炉)坂本雅昭	
 
98

㏻ᖖ᥇ᢥ

CO1-4The Role of Human Oxidation Resistance 1 (OXR1) in Cellular Response to Radiation

A. Matsui, Y. Yoshikawa, A. Yamasaki, T. Saito1, N.
Fujii1, K. Tano1, Q. Zhang-Akiyama

Cell cycle analysis
Nuclei were stained with 50 ug/mL PI. The samples
were analized with FACS.
Targeted disruption of OXR1 in DT40 cells
We prepared chicken OXR1 disrubtion constructs using
puromycin, blasticidin or histidinol resistance gene. The
chicken B lymphoma cells DT40 are cultured andtransfected with the three gene disruption constructs.

Graduate School of Science, Kyoto University
Research Reactor Institute, Kyoto University

1

INTRODUCTION:OXR1 (oxidation resistance 1) isa gene highly conserved in eukaryotes. Previous studies
showed that human OXR1 suppressed spontaneous
mutation in E. coli mutH nth [1]. OXR1 is induced byoxidative stresses such as H2O2 and is localized tomitochondria [2]. However, the function of OXR1
remains to be elucidated. Reactive oxygen species (ROS)
act as a mediator of ionizing radiation -induced cellular
damage. To clarify the protective functions of OXR1
against oxidative damage, we studied the effects of
OXR1 on radiation -generated damage. In this study, weused gamma -ray and high LET heavy -ion beams, which
are known of stronger cell killing effect than X -rays (3).
Our studies showed that OXR1 proteins in HeLa cells
were induced by carbon -ion beam, and that OXR1knockdown HeLa cells were highly sensitive to heavy-ion beams. This year, we found higher micronucleus
formation rate in the cells after irradiation. Then, thecells were released from cell cycle check point earlier
than control cells. To study the function of OXR1 further,
we are now under constructing OXR1-knockout DT40
cells.

RESULTS: The chicken OXR1 targeting constructs,
OXR1-pur, OXR1-bsr and OXR1-his were generated.
DT40 cells are now transfected with electroplation
method. OXR1 -knockout DT40 cells are not gained.
FUTUREPERSPECTIVE:
We
will
try
constructing OXR1 -knockout TD40 cells. After
finishing the step, we will study radation–induced ROS, DNA damages and cell death ofthe construcded cells.

（a）BglII%↓
2%kb%
5’%arm4%kb
XbaI%!
0.8%kb

PvuII!

EcoRI%!

EXPERIMENTS:
Irradiation
HeLa cells stably expressing shRNA targeting OXR1 or
luciferase were synchronized at G1/S phase, andirradiated with gamma -ray (0.77 Gy/min), carbon -ion
(290MeV/nucleon,
87.0keV/um)
or
iron
-ion
(500MeV/nucleon, 64.83 mmH2O) beams generated
by the Heavy Ion Mediacl Accelerator in Chiba(HIMAC). The irradiated cells were incubated（ b）% Puro(3%kb)%%or%%Bsr(4%kb)%%%%%%%%or%His%(5kb)%%

3.13 + cassette kb

BglII%!

3’%arm
1%kb

NotI

5’ arm + pSTBlue-1 + 3’arm = 9kb

3.597 kb

SalI

Fig. 1. (a) Schematic representation of the OXR1 disruption
constructs. (b) Electrophoresis of three constructs.

REFERENCES:[1] M.R. Volkert et al., Proc. Natl. Acad. Sci., (2000)
97, 14530-14535.
[2] N.A. Elliott, M.R. Volkert, Mol. Cell Biol., (2004) 24,
3180-318.
[3] M. Suzuki et al., Int. J. Radiat. Oncol. Biol. Phys.,(2000) 48, 241–250

for about 24 or 34 h, and fixed. The cells wereused in the following experiments.
Micronucleus formation
The nuclei were counter -stained with DAPI.
The
micronuclei
were
detectedwithfluorescence microscopy.

通常採択
採択課題番号 260 1 8
酸化ストレス誘導性タンパク質 OX R1 の機能解析
共同通常（京大院・理）秋山 秋梅、松井 亜子、吉川 幸宏、山崎 晃 (京大・原子炉)田野 恵三、
齊藤 毅、藤井 紀子

99CO1-5Development of an Advanced Optical Fiber Type Neutron Detector

K. Watanabe, Y. Kumagai, A. Uritani, A. Yamazaki,
Y. Sakurai1 and H. Tanaka1

Reactor (KUR). One of the reasons of decrease of thepeak pulse height is expected to be reduction of thetransmittance of the optical fiber. We, therefore, irradiated neutrons to the optical fiber used in our detector.
The neutron flux was 109 n/cm2/s. We continuously
measured the transmittance of the optical fiber by using aspectrometer during the neutron irradiation. The transmittance of the fiber T(t) decreases as;

Graduate School of Engineering, Nagoya University
1
Research Reactor Institute, Kyoto University
INTRODUCTION:
The Boron Neutron Capture
Therapy (BNCT) has been developed as one of thepromising radiotherapies. In this radiotherapy, the neutron dose evaluation is quite important. Therefore, weare developing a novel small neutron flux monitor using
an optical fiber. A small size optical fiber type neutron
detector is one of the promising candidates of the on-line
small neutron flux monitors in BNCT. The conventional optical fiber neutron detectors, however, show no peak
shape corresponding to the neutron absorption reactions,in a pulse height spectrum due to the non-uniform and/or
poor light collection [1-3]. These conventional detectors used ZnS-LiF, Li glass or plastic scintillators. On
the other hand, we apply a new neutron scintillator
Eu:LiCaAlF6. This scintillator has some excellent
properties, such as high light yield, high lithium content,transparency and chemical stability. The light yield of
this scintillator is approximately 5 times higher than thatof the Li glass.
Figure 1 shows the conceptual drawing of the small
size optical fiber type neutron detector. Features of ourdetector are use of a bright scintillator and a quite small
scintillator size. The scintillator size is controlled larger
than ranges of 6Li(n,t) reaction products and smaller than
ranges of fast electrons induced by gamma rays to suppress the signal pulse height only for gamma-ray induced
events.

T t   T0 exp  t /  
where T0; initial transmittance, ; life time of the opticalfiber. We can determine the lifetime by fitting thisequation to the experimental data of decrease of the optical fiber transmittance. Figure 2 shows the wavelength dependence of the lifetime of the optical fiber under neutron irradiation with 109 n/cm2/s. The lifetime ininfrared region is confirmed to be longer than that in ultraviolet and visible region. The emission wavelengthof the Eu:LiCaAlF6 scintillator is 380 nm, where the lifetime of the transmittance is not so long. From theseresults, one of the reasons of decrease of the peak pulse
height is confirmed to be reduction of the transmittanceof the optical fiber.

-1
減衰定数(s)Lifetime (s)107

HV
Optical fiber

PMT

MCA

400

500

600

700

800

波長(nm)
Wavelength
(nm)

Amp.

Fig. 2PC

Fig. 1

105
104
300

Preampscintillator

106

Wavelength dependence of the lifetime under
neutron irradiation.

In infrared region, the neutron radiation hardness isquite high. If we can use a neutron scintillator with
infrared emission, the radiation hardness of the opticalfiber type neutron detector can be improved.

Conceptual drawing of the optical fiber typeneutron detector.

So far, we evaluated dynamic range and long term stability of our detector. Our detector was confirmed toshow good linearity up to 109 n/cm2/s. However, peakpulse height decreases due to neutron irradiation. In
this report, we experimentally evaluate neutron radiation
hardness of the developed detector.
RADIATION HARDNESS TEST: We fabricated theoptical fiber type neutron detector using a small
Eu:LiCaAlF6 scintillator and experimentally evaluated its
radiation hardness at the Heavy Water Neutron Irradiation Facility (HWNIF) of Kyoto University Research

REFERENCES:[1] M. Ishikawa et al., Appl. Rad. Isotopes, 61 (2004)
775-779.
[2] M. Ishikawa et al., Nucl. Instr. Meth. A, 551 (2005)
448-457.
[3] Y. Ito et al., Radiat. Prot. Dosim., 110 (2004)
619-622.

採択課題番号 26021 極小検出器を用いた中性子計測手法の高度化に関する研究
共同通常
通常採択
（名大・工）瓜谷章、渡辺賢一、山﨑淳、熊谷洋祐 （京大・原子炉）櫻井良憲、田中浩基
100CO1-6Focusing Test of an Ellipsoidal Neutron Mirror with a Metal Substrate

M. Hino1, J. Guo2, S. Takeda3, T. Oda1, S. Morita2*,
J. Kato2, Y. Yamagata2, M. Furusaka3, Y. Kawabata1
1
Research Reactor Institute, Kyoto Univ., Japan
2
RAP, RIKEN, Japan,
3
Grad. Sch. of Eng., Hokkaido Univ., Japan*
Present address: Tokyo Denki Univ. Japanneutrons without supermirror coating.
EXPERIMENTS: The design, manufacturing andpolishing of the mirror were carried out by RIKEN [1].
The form accuracy of the mirror was estimated to be
5.3 μm Peak-to-Valley (P-V) and 0.8 μm P-V for theminor-axis and major-axis direction respectively,
while the surface roughness was reduced to 0.2 nm
rms. The neutron focusing performance of the mirror
was evaluated using CN3 beam line at Kyoto
University Research Reactor (KUR-CN3).
RESULTS: As shown in Fig.1, the two-dimensional(2D) image of neutron beam reflected by an ellipsoid
focusing mirror was clearly changed as a function of
distance between the mirror center and detector.
Cadmium (Cd) pinhole with an aperture size of 1 mm
in diameter to choose incident beams from the CN3
guide a Cd U-shape slit to remove unnecessary
neutron beams affecting the focusing. The circularfocusing spot at the focal point was almost equivalent
to that of the pinhole.
REFERENCES:[1] J.Guo, et al., Optics Express,
22(2014)24666-24677.

INTRODUCTION: Progress of neutron opticaldevices is significant, however, it is still very difficult
for neutron aspherical focusing mirror. Because therequired surface roughness is smaller than 0.5 nm
even for m=3 supermirror coating and the mirror sizeis large. In order to realize large ellipsoid neutron
focusing mirror, we are doing several trials. In thisstudy, we show the neutron focusing experimental
result of ellipsoid mirror with a metal substrate. In
general it is very difficult to make a smooth surface on
metal due to the grain structure. By using electrolessnickel-phosphorus (NiP) plated material, we canovercome this problem. Electroless NiP has great
advantages for realizing neutron mirror because of its
amorphous structure, good machinability andrelatively large critical angle of total reflection for

Fig.1 Schematic layout of neutron focusing experiment at KUR-CN3 and the 2D images of beam shapes as a functionof the mirror center to detector distance (MDD), and the direct beam shape without the focusing mirror at the focal
point.

採択課題番号 26065
次期中性子ビーム科学施設のための中性子光学デバイス開発 共同通常
通常採択
Fig.2 Measured reflectivity of the m=5 flexible NiC/Ti supermirror sheet bounded on flat plate.
（京大・原子炉）日野正裕、小田達郎、川端祐司 （KEK・IMSS）山田悟史、遠藤仁、瀬戸秀紀（理研）郭江、森田晋也、加藤純一、山形豊 （北大）武田晋101

CO1-7

Examination of the Usefulness as the New Boron Compound of KA-BSH
for Born Neutron Capture Therapy

Gen Futamura1, Shinji Kawabata1,
Shin-Ichi Miyatake2, Toshihiko Kuroiwa1,
Yoshihide Hattori4, Mitsunori Kirihata4, Hiroki Tanaka3,
Yoshinori Sakurai3, Shin-Ichiro Masunaga3, Koji Ono3

travenous administration (iv) and neutron irradiated;
Group 2, KA-BSH administered by convection enhanced
delivery (CED) by using Alzet pump, which can deliver
solutions directly into the solid tissue with continuouspressure gradient distribution [2, 3], and neutron irradiated; Group 3, neutron irradiation; Group 4, untreatedcontrols. BNCT was initiated 1 h after termination of
Alzet pump infusion or i.v. administration. All irradiated rats were anesthetized with a pentobarbital sodium.
The rats were irradiated for 60 min with 1MW. The
antitumor effects of BNCT were evaluated in the mean
survival times (MSTs) of the rat.

1

Department of Neurosurgery, Osaka Medical College
Division for Advanced Medical Development, Cancer
Center, Osaka Medical College
3
Research Reactor Institute, Kyoto University
4
Osaka Prefecture University

2

INTRODUCTION:
Boron neutron capture therapy (BNCT) is an attractive
technique for malignant brain tumor treatment. [1] It is
important to have a significant differential uptake of 10B
between tumor cells and normal cells to achieve potent
tumor-selective antitumor effects.
Today, clinicallyused dodecaboranethiol (BSH) is transferred to brain tumors only through the disrupted blood-brain barrier(BBB), so it is difficult for BSH to reach regions thattumor cells invade microscopically where the BBB seems
to be normal. On the other hand, boronophenylalanine(BPA), which transfers boron via L-type amino acidtransporter, can deliver 10B even in the infiltrating tumor
cell population where the BBB is normal. However,some amounts of 10B are inevitably taken into the normal
cells by BPA systemic administration. A wide variety ofboron delivery agents have been synthesized to solvethese problems. [1] Kojic acid (KA) was reported as theagent which showed intense uptake in malignamt tumor.
Therefore, we designed and synthesized KA-BSH andevaluated therapeutic effect of KA-BSH as boron delivery agents for BNCT in F98 glioma cell bearing rat brain
tumor model.

RESULTS:The estimated physical radiation doses delivered to tumor,
brain and blood were calculated according to boron concentrations. The physical radiation doses delivered tothe tumor were 1.1Gy for KA-BSH administered by iv.
The corresponding normal brain doses were 1.0Gy. The
survival data of Group 1, 2, 3 and 4 following BNCT
showed that the MSTs were 35.4±8.0 days, 29.8±3.3 days,
30.2±2.2 days and 28.5±3.1 days, respectively.
We accepted significantly extend the duration of survival
time of the rats group using KA-BSH administered by iv(Group 1), compared with the neutron irradiation only
(Group 3) (p<0.005).

CONCLUSION:
Survival times of group1 were significantly prolonged
even compared with irradiation group. The therapeutic
effect of KA-BSH administered by iv was higher thanthat we expected from these tissue boron concentrations
and physical radiation doses. This study suggested that
KA-BSH might have extremely high compound biological effectiveness (CBE), and KA-BSH might be the drug
to add therapeutic effect of clinical BNCT using BPA orin combination with BPA / BSH to.

MATERIALS AND METHODS:
BNCT was performed 14 days following stereotactic implantation of 103 F98 glioma cells implanted rat brain
tumor model. Rats were transported to the Nuclear Reactor Laboratory at Kyoto University Research Reactor
Institute.
Based on the results of the biodistribution study, we prepared 4 groups. The rats were then randomized on thebasis of weight into experimental groups of 6-8 animals
each as follows: Group 1, KA-BSH administered by in-

REFERENCES:[1] Barth RF et al: Radiat Oncol 7: 146, 2012.
[2] Hiramatsu R et al: J Pharm Sci 104: 962-70, 2015
[3] Kawabata S et al: J Neurooncol 103: 175-85, 2011

採択課題番号 26078
新規硼素化合物の有用性と腫瘍幹細胞の克服
通常採択（大阪医大）黒岩敏彦、宮武伸一、川端信司、二村元、東保太一郎、木村誠吾、大村直己（岡山大）道上宏之（京大原子炉）増永慎一郎、小野公二
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