ANNUAL REPORT2018 - 2019
Volume 1

CONTENTS
Preface––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– 3
Organization–––––––––––––––––––––––––––––––––––––––––––––––––––––––––– 4
Division of Science–––––––––––––––––––––––––––––––––––––––––––––––––– 5
Division of Education–––––––––––––––––––––––––––––––––––––––––––––––– 7
Division of Safety Management–––––––––––––––––––––––––––––––––––––––– 9Radioisotope Research Center––––––––––––––––––––––––––––––––––––––––– 11I

Targeted Alpha-particle Therapy Research Project
At project

211

Synthesis and Evaluation of Astatine-211-labeled Gold Nanoparticles
as Targeted Alpha-particle Therapy

15

Investigation of Novel Drug for Alpha-emitting Nuclear Medicine Targeting
to Cancer Specific Amino Acid Transporter, LAT1

16

Y. Kadonaga, X. Huang, A. Shimoyama, K. Kabayama, Z. Zhang, Y. Manabe, K. Fukase

K. Kaneda-Nakashima, Y. Manabe, A. Shimoyama, K. Kabayama, T. Watabe, Y. Kanai, K. Ooe, A. Toyoshima,
Y. Shirakami, T. Yoshimura, M. Fukuda, J. Hatazawa, T. Nakano, K. Fukase, A. Shinohara

Measurement of Dispersal Rate of At-211 from Aqueous Solution

17

K. Nagata, K. Shirasaki, A. Toyoshima, K. Ooe, A. Shinohara, T. YoshimuraStudies on Synthesis and QC Test Methods for Low Molecular Compounds Labeled with 211At

Y. Shirakami, K. Kaneda-Nakashima, T. Watabe, Y. Liu, K. Ooe, A. Toyoshima, A. Shinohara, E. Shimosegawa, J. Hatazawa

Stable and periodic supply of purified 211At samples
for the research project on development of targeted alpha therapy

A. Toyoshima, K. Ooe, T. Teramoto, K. Nagata, Y. Kon, S. Ichimura, H. Obata, A. Kanda, S. Nakagawa, T. Yoshimura,
M. Fukuda, A. Shinohara

Development and Evaluation of Astatine-211 Conjugated Anti-CD20 Monoclonal Antibody
K. Kabayama, K. Kaneda-Nakashima, Y. Manabe, A. Shimoyama, A. Toyoshima, A. Shinohara, K. Fukase

18

19

20

Adsorption Behavior of Volatile Astatine (At) Compounds Observedwith Developed Thermochromatograph Apparatus

21

Determination of Ionic Radius of Astatide (At-) in Aqueous Solutions

22

S. Ichimura, A. Toyoshima, K. Ooe, T. Teramoto, K. Nagata, H. Obata, A. Kanda, S. Nakagawa, T. Yoshimura, A. Shinohara
H. Obata, K. Ooe, T. Teramoto, T. Yoshimura, A. Toyoshima, A. Shinohara

Targeted Alpha Therapy Using At-211 NaAt for the Refractory Differentiated Thyroid Cancer
T. Watabe, K. Kaneda-Nakashima, Y. Liu, Y. Shirakami, K. Ooe, A. Toyoshima, E. Shimosegawa, M. Fukuda,
A. Shinohara, J. Hatazawa

23

Ac project225

Supply of 225Ac Separated from 229Th Generator to Develop Targeted Alpha Therapy

24

Theranostics Targeting Fibroblast Activation Protein:
Cu-64 and Ac-225 labelled FAPI-04 in Pancreatic Cancer

25

A. Toyoshima, H. Kikunaga, K. Shirasaki, K. Nagata, K. Tsukada

T. Watabe, Y. Liu, K. Kaneda-Nakashima, Y. Shirakami, T. Lindner, K. Ooe, A. Toyoshima, K. Nagata, E Shimosegawa,
U. Haberkorn, C. Kratochwil, A. Shinohara, F. L. Giesel, J. Hatazawa

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Volume 1

II

Research Activity
Carcinogenicity and Genome Variation in Descendant Mice after the Every Generational Low Doserate Internal 137Cs Radiation Exposure (Fukushima and Chernobyl Simulation Experiment)

27

H. Nakajima

Training Course of Handling Radioisotopes for Medical Students

28

H. Nakajima, T. Fujiwara

Fine Structural Analysis of Surface with Electron Diffraction

29

M. Okada

Development of the New Radiation Monitoring System Using DNA as a Radiation Sensor

30

K. Shimizu, Y. Matuo, M. Yamaguchi, Y. Izumi

Anion-exchange Experiment of Superheavy Element, Dubnium, Together
with its Homologs Nb and Ta and Pseudo-homolog Pa

31

A. Toyoshima, S. Adachi, K. Tsukada, M. Kato, A. Kashihara, M. Asai, H. Haba, Y. Komori, T. Yokokita, Y. Shigekawa,
D. Mori, Y. Wang, A. Nakajima, Y. Suzuki, K. Nishizuka, K. Tokoi, K. Sueki

Synthesis and Properties of Thiohalidecapped Hexanuclear Technetium Complexes

32

T. Yoshimura, K. Nagata, Y. Kino, T. Takayama, T. Sekine, A. ShinoharaAnion-exchange of Zr, Hf, and Th in HNO3 with the Automated Extraction Apparatus:
toward the Chemical Study of Rf

33

Y. Kasamatsu, E. Watanabe, T. Yokokita, S. Hayami, K. Tonai, Y. Shigekawa, H. Haba, A. Shinohara

Maintenance of Chromosomal DNA in Eukaryotic Cells

34

A. K. Okita, T. Nakagawa

Performance Study on new Front-end ASIC of Pixel Detector
for High-Luminosity Upgrade of the ATLAS experiment35

Identification of 90Sr and Plutonium Isotopes
from the Radioactive Particles Released from the Accident of FDNPP

36

M. Hirose, H. Nanjo

K. Ninomiya, J. Igarashi, Z. Zhang, T. Kajiwara, M. Matsuda, Y. Yamaguchi, A. Shinohara

New Electromagnetic Calorimeter with a Photon/Neutron Discrimination Power37

H. Nanjo, T. Yamanaka

Current Interstitial Brachytherapy for Tongue Cancer

38

S. Murakami, Y. Iwamoto, T. Tsujimoto, K. Marutani

Estimation of Background Gamma-ray Spectrum for High-precision Dosimeter for Future Fukushima
I. Murata, J. Angxuan, S. Tamaki, S. Kusaka, F. Sato

Fabrication of Radiophotoluminescence Dosimeter with 3D-printing Technology

40

F. Sato, T. Hashimoto, S. Tamaki, S. Kusaka, H. Miyamaru, I. Murata

Irradiation Induced Amorphization in High Entropy Alloys

41

T. NagaseIII

39

Achievements
Original Paper

43

Biblio52

Presentation

53

Award

62

Social Contribution

62

Fund for Preparation of New Education and Research Projects

63

Name Index–––––––––––––––––––––––––––––––––––––––––––––––––––––––––– 68
IRS ANNUAL REPORT

2018-20192

Preface
It is our pleasure to present Annual Report 2018-2019 of Institute for Radiation
Sciences (IRS), Osaka University.
IRS was established in 2018 in Osaka University to reinforce education, research,and safety management relating to radiation sciences. IRS is the unique department
utilizing open-minded advantages of Osaka University by unifying all the radiation
facilities in the university. At present, in particular, we are developing the Targeted
Alpha Therapy by collaborating with basic science groups (in Graduate Schoolof Science, etc.), an accelerator facility (in Research Center for Nuclear Physics),
and Osaka University Hospital, by the research and development project based on
the budget, “Promotion of nuclear-medicine innovation by the establishment ofInstitute for Radiation Sciences” (FYs 2018-2022).
This annual report summarizes our scientific achievements in the first two years(2018-2019) since IRS was established. I sincerely hope that these achievements
will inspire further advances, promote worldwide collaborations with our scientists
in IRS, and ultimately contribute to achieve the only one unique outcomes andvalues which can be obtained only in Osaka University.
October 2020

OGAWA, Tetsuo, Ph.D.
Director
Institute for Radiation Sciences
Osaka University

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IRS ANNUAL REPORT

2018-2019

Organization

Steering
Committee
Division of Science

Director

DeputyDirector

Institute
Committee

Division of Education

Division of
Safty Management

Radiation Facility of
Each Department*1, *2

Management Ofﬁce ofEach Radiation Facility

Radioisotope
Research Center*1 Radiation-related facilities(1) Radio Isotope Experiment Laboratory,
		 Graduate School of Science * Note(2) Radiation Science Experiment Laboratory,
		 Graduate School of Science * Note(3) Radioisotope Usage Facility,
		 Graduate School of Medicine(4) Radioisotope Usage Facility, Division of Health Science,
Graduate School of Medicine(5) Radioisotope Medical Care Facility,
		 Osaka University Hospital(6) Radioisotope Medical Care Facility,
		 Osaka University Dental Hospital(7) Radioisotope Usage Facility,
		 Graduate School of Engineering(8) Radiation Generator Usage Facility,
		 Institute of Free Electron Laser,		 Graduate School of Engineering(9) Radioisotope Usage Facility,
		 Graduate School of Frontier Biosci­ences(10) Radio Isotope Experiment Laboratory,
		 Research Institute for Microbial Diseases(11) Radioisotope Usage Facility,
		 The Institute of Scientific and Industrial Research(12) Radioisotope Usage Facility,
		 Institute for Protein Research(13) Radioisotope Usage Facility,
		 Institute of Laser Engineering Usage Facility of		 Ultra-high Voltage Electron Microscope Selective(14) Radiation Generator(15) Radioisotope Usage Facility,
		 Radioisotope Research Center (Suita branch)(16) Radioisotope Usage Facility,
		 Radioisotope Research Center (Toyonaka branch)(17) Radioisotope Usage Facility,
		 Nuclear Physics Research Center*2 Nuclear Fuel Usage Facility(1) Department of		 Sustainable Energy and Environmental Engineering,
		 School of Engineering(2) Radiation Science Experiment Laboratory,
		 Graduate School of Science

Note: Integrated with RI Radioisotope Research Center (Toyonaka branch) from April 1, 2018

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Division of Science

Members and 52 concurrent post members
Professor

Specially Appointed Prof.

Specially Appointed Prof.

Specially Appointed Prof.

Spec. App. Assoc. Prof.

Spec. App. Assoc. Prof.

Spec. App. Assoc. Prof.

Spec. App. Assist. Prof.

FUKASE, Koichi

TOYOSHIMA, Atsushi

TERAMOTO, Takahiro

YONEKURA, Yoshiharu

SHIRAKAMI, Yoshifumi

GIESEL, Frederik L.

KANEDA-NAKASHIMA, Kazuko

KADONAGA, Yuichiro

Goals and Objectives
In Division of Science, towards our final goal of a clinical trial using astatine-211 (211At) at
Osaka University Hospital, objectives in 2018-2019 were set as follows.
• Development of a regular supply system of 211At• Development of an automated separation apparatus of 211At• Development of targeting molecules and labeling methods with 211At• Pharmacological tests and biological evaluation of developed 211At pharmaceuticals• Decision of primary candidate of pharmaceutical for the clinical trial

Achievements
In these years, we developed a regular supply system of 211At. In 2019, because of the
improvement of cyclotron at RCNP, we were regularly supplied 211At from RIKEN Nishina
Center for Accelerator-Based Science based on Material Transfer Agreement between
RIKEN and Osaka University. We also obtained 211At via the short-lived RI supply platform.
Using supplied 211At in aqueous water, a variety of pharmaceuticals were developed
and pharmacological and biological tests have been carried out. The followings are therepresentative results.

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IRS ANNUAL REPORT

2018-2019https://www.irs.osaka-u.ac.jp/department/science_mission.html• For K1-NIS (sodium/iodide symporter) tumor xenograft mice, we clearly observed theenhanced uptake of 211At by thyroid under conditions where ascorbic acid was added. The
K1-NIS tumors showed significant accumulation of 211At. Tumor growth was immediately
inhibited in a dose-dependent manner after administration of 211At. In the survival analysis,the 211At group showed significantly better survival than the control group. We decided[211At]-NaAt as our primary candidate for the clinical trial.
• Various amino-acid derivatives such as α-methyl-tyrosine, which targets L-type amino-acidtransporter 1 (LAT1) have been successfully labeled with 211At. Specific uptake by humanpancreatic cancer cell PANC-1 in-vitro was showed. Moreover, for cancer-bearing mice, aremarkable anti-tumor effect was observed.

Selected Publications(double underline for full-time staff and single underline for external staff of IRS)
Theranostics targeting fibroblast activation protein in the tumor stroma:
64Cu- and 225Ac-labelled FAPI-04 in pancreatic cancer xenograft mouse models
T. Watabe, Y. Liu, K. Kaneda-Nakashima, Y. Shirakami, T. Lindner, K. Ooe, A. Toyoshima, K. Nagata, E. Shimosegawa,
U. Haberkorn, C. Kratochwil, A. Shinohara, F. Giesel, J. Hatazawa
J. Nucl. Med. (2019) First published October 4. DOI: 10.2967/jnumed.119.233122

Dispersal rates of astatine-211 from aqueous solutions and chloroform

A. Toyoshima, K. Nagata, K. Ooe, Z. Zhang, T. Ikeda, S. Ichimura, H. Obata, T. Yoshimura, A. Shinohara
Radiat. Safety Management, 18 (2019), 16-22. DOI: 10.12950/rsm.190423

Quantitative measurement of 219Rn radioactivity in exhaled breath from patientswith bone metastasis of castration-resistant prostate cancer treated with 223RaCl2
K. Ooe, T. Watabe, T. Kamiya, T. Yoshimura, M. Hosono, A. Shinohara, J. Hatazawa
EJNMMI Phys. 6 (2019), 13-1-11. DOI: 10.1186/s40658-019-0249-8

Radiotheranostics coupled between an At-211-Labeled RGD peptide
and the corresponding radioiodine-labeled RGD peptide
K. Ogawa, T. Takeda, K. Mishiro, A. Toyoshima, K. Shiba, T. Yoshimura, A. Shinohara, S. Kinuya, A. OdaniACS Omega, 43 (2019), 4584-4591. DOI: 10.1021/acsomega.8b03679

Enhancement of astatine-211 uptake via the sodium iodide symporterby the addition of ascorbic acid in targeted alpha therapy of thyroid cancer
T. Watabe, K. Kaneda-Nakashima, Y. Liu, Y. Shirakami, K. Ooe, A. Toyoshima, E. Shimosegawa,
M. Fukuda, A. Shinohara, J. Hatazawa
J. Nucl. Med. 60 (2019), 1301-1307. DOI: 10.2967/jnumed.118.222638

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Division of Education

Members and 27 concurrent post members
Professor

NOMACHI, Masaharu

Professor

OKADA, Michio

Assocciate Prof.

NAKAJIMA, Hiroo

Division of Radiation Education promotes the education of radiation sciences across the
University. Combining campus wide activities on human resource development, program
can be proceeded more efficiently. It also helps to make high-level program and international
program.
Osaka University set up “Graduate Programs for Advanced Interdisciplinary Studies” that
could provide motivated students with an opportunity to master the basics in a wide rangeof fields while focusing on an advanced specialty. Radiation-related programs include theGraduate School of Medicine’s “Advanced cancer professional development programs” and“Radiation science”. “Radiation science” has been implemented as a program by our Institutefrom this fiscal year with the cooperation of Research Center for Nuclear Physics, Graduate
School of Science, and Graduate School of Medicine. In the future, we will develop it as thecore educational program of our Institute.
Division of Radiation Education provided “Natural sciences, sociology, and humanities related
to radiation” as a basic liberal arts subject of general education in Osaka University.
This subject is open to all faculties and grades and offers cross-disciplinary study of radiationrelated physics, chemistry, biology, medicine, law, economics, and social psychology.
The science and humanities students were educated so that they could understand radiationfrom various angles and become facilitators for risk communication. This year, 32 students inscience and humanities attended. We will continue this and enhance it from next year onward.
Division of Radiation Education organizes International schools on radiation measurements.
Students from Vietnam, Malaysia and Indonesia are invited to the school with a supportof JST SAKURA Science plan. In 2018, 10 days from 31 October, 18 students and 2 staff
members were invited. In 2019, 10 days form 21 November, 18 students and 2 staff members
were invited. Exercises for radiation measurements were prepared. They also visited Kamioka
underground laboratory.

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2018-2019https://www.irs.osaka-u.ac.jp/department/education_mission/

The school were also held outside Japan. Collaboration with IEEE/NPSS, Realtime school forradiation measurements. In 2018, the school was held 11 days from 7 July in Cape Town. Morethan 50 students participated. In 2019, the school was held 6 days from 15 November in Kuala
Lumpur, Malaysia. 24 students were invited. The school was supported also by KEK. In 2020,
two schools were held. One school is 3 days from 9 November in Indonesia. Another one is 3
days from 3 December in Dakar, Senegal. Because of the pandemic of Covid-19, both schools
were held remotely. We did not make exercises but did make demonstration. However, we got
more than 200 participants in Indonesia school.
In those schools, exercises take very important roll. Recent development of electronics allows
us to make compact and cheap but high-performance system. We are collaborating for thedevelopment of educational equipment with IPMU, PSI, IEEE/NPSS and Ho Chi Minh city
science University.
These activities were reported at international conference ANIMMA (Advancements inNuclear Instrumentation Measurement Methods and their Applications) 2019.
In 27-28 March 2019, Workshop on “Interdisciplinary approach of applying cutting-edge
technologies at the frontier of cancer research” was held in Osaka University, Nakanoshima
center. Medical applications and human resource development on those fields were discussed.
The Osaka University Co-Creation Day @ EXPOCITY was held on Saturday, November 30,
2019 at LaLaport EXPOCITY with the aim of deepening exchange between corporations, local
municipalities, and regional society. We set up the booth “What can we do with radiation?”on the day of the event in order for attendees to learn more about cutting-edge knowledge,
research results, and valuable materials concerning the radiation sciences. There were also
“hands-on” experiences for children, with faculty, staff, and students explaining the activities inan easy-to-follow format. The 389 attendees visited our booth and also enjoyed a sticker rally.
We aim at International Education Center for Radiation Science. The rooms for school in a newbuilding, which will be build 2021, will makes it easy to organize a school.

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Division of Safety Management

Members and 27 concurrent post members
Professor

YOSHIMURA, Takashi

Assistant Prof.

SUZUKI, Tomokazu

Technical Staff

KON, Yukiyoshi

Division of radiation safety management works together with radiation facilities and nuclear
fuel facilities with respect to radiation safety management and sums up radiation safety
management in our university. Radioisotope research center undertakes a role of the centerof the division and liaises closely with staffs of the facilities. The risk management system isconstructed that the staffs of the institute cooperate and support to settle an emergency andaccident and to provide information of the situation.

Achievements

Workshop on educational program of radiation safety
management skill upgrading for university staffs
The seven isotope research centers in the national universities have conducted the workshop
supported by Nuclear Regulation Authority, Japan. In 2018, the workshop was held in Osaka
University. The 59 attendances participated in the workshop. The keynote lecture was held
on revision of radiation protection rules, and the contents of the rules were discussed. In
addition, the participants did model programs of radiation practical training, and the contents
and improvement were discussed. In 2019, the workshop was held in Kyoto University. The
attendances were 36.

Workshop on radiation education and training for use of alarge-sized accelerator facility toward amendment of the law
Each facility can define number of hours to radiation education and training for new radiation
workers by amendment of the law concerning protection of radiation hazards. When they use
an off-campus large-sized accelerator, it needs to accommodate on what kind of education andtraining they should take on the sending and receiving facilities. In the workshop, persons
in various positions gave presentation on the education and training, and the future wasdiscussed.

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Workshop on protection of specific radioisotopes
Workshop on protection of specific radioisotopes was held with Radiation Safety Councilof Universities in Japan in 2019. In the workshop, radiation regulation division in Nuclear
Regulatory Agency, Japan lectured. There was a question-and-answer session among thelecturer, panelist, and audience.

OthersIn 2019, a working group prepared a draft for revision of the regulations for prevention ofradiation hazards with the amendment of the law. Each radiation facility in the university was
required to amend the radiation protection rules, and upon request, the proposed revisions
were checked by the division of radiation safety management. The division of radiation safety
management cooperated with the radiation safety subcommittee of the nuclear research andsafety committee, Osaka University to conduct radiation safety management inspections of theradiation facilities on the campuses.

Selected Publications
1) Takashi Yoshimura, Introduction to Radiation Education and Radiation Safety Management
Network That Is Mainly Composed of Isotope Centers for Decent Radiation Protection, Jpn.
J. Radiat. Saf. Manage., 17, 77-78 (2018) in Japanese.
2) Tomokazu Suzuki, Hiroshi Watabe, Hidetoshi Kikunaga, Hiromitsu Haba, and Mitsuhiro
Fukuda, The Legal Procedure under Act on Prevention of Radiation Hazards Due toRadioisotopes, etc. for Realization of Supply Platform of Short-lived Radioisotopes for
Fundamental Research, Jpn. J. Radiat. Saf. Manage., 17, 121-124 (2018) in Japanese.

IRS ANNUAL REPORT

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Radioisotope Research Center
Members and 16 concurrent post members
Professor

Professor

Assistant Prof.

Technical Staff

TOMIYAMA, Noriyuki

NAGATA, Kojiro

YOSHIMURA, Takashi

Assocciate Prof.

SHIMIZU, Kikuo

YAMAGUCHI, YoshiakiRadioisotope Research Center (RI center) has buildings in Suita and Toyonaka campuses. RI
center Suita is a main building, and this building is a core facility of Institute for Radiation
Sciences. RI center Toyonaka is a branch. In RI center Suita, the research of alpha-particle
nuclear therapy project has conducted. As the accelerator in RCNP is now in under versionup, 211At produced in RIKEN and QST Takasaki transported to RI center Suita, and thenseparation from an irradiated target material, purification of 211At, syntheses of labelled
compounds, and animal experiments were performed in the center. The research using 225Ac
has recently started.
In 2019, the radiation-controlled area in RI center Suita was enlarged and the ability of air
exhaust in the working rooms was improved. The purpose of the improvement is to supply
the separated and purified 211At for a radiopharmaceutical in the university hospital and to
make the facility more accessible to off-campus users. In the working rooms which were newly
included in the radiation-controlled area, the amount of usage for 211At is up to 2 GBq/day. The
SPECT system has installed in the working room on the first floor of the center and the abilityof air exhaust increases one and a half times more, which allow us to use a greater number ofradionuclides and a greater quantity of them.
We have established an organization and responsibility system for conducting the test inaccordance with the reliability standards in the law. The system involves many staffs who use
RI center Suita for Alpha-particle nuclear therapy project in our institute.

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2018-2019https://www.irs.osaka-u.ac.jp/department/ri_mission.html

RI center has been operated as an on-campus facility. For this reason, off-campus users had
to have on-campus status to use the facility. The system is not convenient; therefore, we haverevised the rules so that people who do not have an on-campus status can use the facilities.
We have also set new user fees for off-campus users. In addition, we have prepared two newworking rooms (26 m2 each) for off-campus users. One of the working rooms is equipped withanimal housing unit. The room (84 m2) with four draft chambers is available for practicaltraining using unsealed radioisotopes.
In 2020 or later, the radiation facility of RI center Suita is scheduled to be integrated with theradiation facility of Graduate School of Medicine. RI center Suita and the radiation facility ofGraduate School of Medicine are located about 100 m apart. Users to utilizing both facilities
are increased with recent progress in the development of alpha-particle nuclear therapy
project. The half-life of 211At is 7.2 hours and it decays in a short period. The amount of 211At is
reduced when the transfer/acceptance and transport procedures between the two facilities takea long time. Therefore, the two facilities are integrated to simplify the hauling process and to
make operation of both facilities more efficient.

Selected Publications
1) Takashi Yoshimura, Kojiro Nagata, Ayumi Matsuda, Toshiki Omote, Yasushi Kino,
Tsutomu Takayama, Tsutomu Sekine, and Atsushi Shinohara, Synthesis Structures, Redox
Properties, and Theoretical Calculations of Thiohalide Capped Octahedral Hexanuclear
Technetium(III) Clusters, Dalton Trans., 48, 14085-14095 (2019).
2) Moe Seike, Kojiro Nagata, Hayato Ikeda, Akitaka Ito, Eri Sakuda, Noboru Kitamura,
Atsushi Shinohara, and Takashi Yoshimura, Synthesis and Photoluminescence ofTetracyanidonitridorhenium(V) Complexes with Five-membered N-Heteroaromatic
Ligands and Pholuminescence-Intensity Change, ACS Omega, 4, 21251-21259 (2019).

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Targeted Alpha-particle Therapy
Research Project

IRS ANNUAL REPORTI

2018-201914

At project

211

Synthesis and Evaluationof Astatine-211-labeled Gold Nanoparticles
as Targeted Alpha-particle Therapy

I
Targeted Alpha-particle Therapy Research Project

KADONAGA, Yuichiro;1 HUANG, Xuhao;2 SHIMOYAMA, Atsushi;2
KABAYAMA Kazuya;2 ZHANG, Zijian;2 MANABE, Yoshiyuki;2 and FUKASE, Koichi1,2*
1 Division of Science, Institute for Radiation Sciences, Osaka University
2 Department of Chemistry, Graduate School of Science, Osaka University* koichi@chem.sci.osaka-u.ac.jp

We focus on the development of targeted alpha-particle therapy (TAT) by using Astatine-211(211At) labeled gold-nanoparticles.
Alpha-particle has high energy to effectively kill cancer cells as compared with beta- or gamma
emission. Additionally, short range of alpha-particle minimizes damage to organs aroundcancer cells. 211At is an attention-grabbing alpha emitting radionuclide because it can be easily
produced from Bismuth-209.
211

At which has similar characteristics to iodine rapidly accumulated into thyroid gland.
Thus, we planned to attach 211At on gold nanoparticles (AuNP) as a method of retaining it
around cancer cells. We initially synthesized several sizes of AuNP (13, 30 and 120 nm) from
HAuCl4·4H2O as a starting material.1 Subsequently, each AuNP was pegylated with methoxy
PEG thiol.2 The quality of pegylated AuNP (AuNP-PEG) was evaluated by transmission
electron microscope (TEM) imaging (Figure 1). The AuNP-PEG in hand, Astatination was
attempted in distilled H2O at room temperature for 5 min to obtain 13, 30 and 120 nm ofastatinated AuNP-PEG (211At-AuNP-PEG) in excellent yield (Table 1). Additionally, desire
211
At-AuNP-PEG was stable in plasma at room temperature for 24 h.
We evaluated cytotoxicity of
At-AuNP-PEG (13, 30 and
120 nm) against Raji cell. As
expected, encouraged cytotoxicity
was observed in all experiments.
211

We next approached to improvecytotoxicity by 211At. Recently,
we also succeeded in them o d i f i c a t i o n o f Au N P w i t hbranched polyethylene imine
and oligosaccharides to enhancecell-uptake of 211At. They can bepromising materials for emittingalpha-particle inside cancer cells.

[1] J. Phys. Chem. C 2011, 115, 4502-4506.
[2] Gold Bull. 2011, 44, 99-105.
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IRS ANNUAL REPORT

2018-201913 nm AuNP-PEG
Magnification 100000 X

30 nm AuNP-PEG
Magnification 100000 X

120 nm AuNP-PEG
Magnification 30000 X

Figure 1. TEM imaging of 13, 30 and 120 nm AuNP-PEG.

At project211

Investigation of Novel Drug for Alpha-emitting
Nuclear Medicine Targeting to Cancer SpecificAmino Acid Transporter, LAT1I
Targeted Alpha-particle Therapy Research Project

KANEDA-NAKASHIMA, Kazuko;1,2* MANABE, Yoshiyuki;2,3 SHIMOYAMA, Atsushi;2,3
KABAYAMA, Kazuya;2,3 WATABE, Tadashi;2,5 KANAI, Yoshikatsu;2,6
OOE, Kazuhiro;2,5 TOYOSHIMA, Atsushi;1,2 SHIRAKAMI, Yoshifumi;1,2,5
YOSHIMURA, Takashi;2,7 FUKUDA, Mitsuhiro;2,8 HATAZAWA, Jun;2,5
NAKANO, Takashi;2,8 FUKASE, Koichi;2,3 and SHINOHARA, Atsushi;2,4
1 Division of Science, Institute for Radiation Sciences, Osaka University
2 MS-CORE, PRC, Graduate School of Science, Osaka University
3 Laboratory for Natural Product Chemistry, Graduate School of Science, Osaka University
4 Laboratory for Radiochemistry, Graduate School of Science, Osaka University,
5 Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University
6 Department of Bio-System Pharmacology, Graduate School of Medicine, Osaka University
7 Radioisotope Research Center, Institute for Radiation Sciences, Osaka University
8 Research Center for Nuclear Physics, Osaka University* kkaneda@irs.osaka-u.ac.jp

Targeted alpha therapy (TAT) is receiving much attention in the field of “Theranostics” becauseof its high cytotoxic effect to the targeting cancer. However, physiological uptakes in nontargeted organs are also observed in the TAT, which might lead to the severe side effects. We
should consider about both maximizing the treatment effect in the tumor and minimizing theside effects in the organs at risk. From this viewpoint, decision of targeting molecule was mostimportant. We selected LAT1 as molecular target. LAT1 is one of the amino acid transporters,
which has highly specificity to cancer tissues (Fig.1). We developed next-generation internal
radiotherapy using chemicals targeting LAT1. First, we synthesized alpha-methyl-L-tylosinelabeled with 211At. 211At was produced by the cyclotron, and then quickly purified and labeled(211At-AAMT). Next, we performed its cytotoxicity evaluation using some cancer cell lines. As
a result, cell death and specificity were confirmed. We also confirmed the specificity in vivo andfound the anti-cancer effects in vivo study. In the immediate future, we will examine that theeffects of 211At-AAMT using several kinds of tumor-bearing models.
We could be validated LAT1 as a molecular target for nuclear medicine. However, ourcompounds are not patentable. Therefore, screening of a new compound was started. On theother hand, problem of our labeling product is its procedure. Our labeling technique of aminoacid is used small amount of mercury. Theoretically, no mercury remains in the product, but
the development of a labeling method that does not use mercury is considered necessary forpractical use. We are now trying to establish new precursor for 211At labeling.

Figure. LAT1 as a molecular target.

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2018-201916

At project211

Measurement of Dispersal Rate of
At-211 from Aqueous Solution
I
Targeted Alpha-particle Therapy Research Project

NAGATA, Kojiro;1* SHIRASAKI, Kenji;2 TOYOSHIMA, Atsushi;1 OOE, Kazuhiro;4
SHINOHARA, Atsushi;1,4 and YOSHIMURA, Takashi1
1 Institute for Radiation Sciences, Osaka University
2 Institute for Materials Research, Tohoku University
3 Graduate School of Medicine, Osaka University
4 Graduate School of Science, Osaka University* nagatak13@rirc.osaka-u.ac.jp

Astatine-211 (211At) which is a heavier analog of iodine, is an alpha-emitting radionuclide
with a half-life of 7.2 h. This nuclide is produced by a cyclotron and used for cancer therapy.
In this report, dispersal rates of 211At from aqueous solutions in various pH conditions were
determined and adsorption property of 211At to glass and charcoal filters was studied, in orderto obtain knowledge on the reduction of internal exposure and proper handling condition.
For the collection of dispersed 211At, an apparatus was made based on the iodine collection
apparatus with glass and charcoal filters. In the container, filter paper and charcoal cartridges
were placed downstream from the air inlet to the order of a glass fiber filter paper, a charcoal
impregnated filter, and two charcoal cartridges. An aqueous stock solution of 211At was
obtained by dry distillation from a Bi target irradiated by an alpha beam using the cyclotron
followed by dissolution to water. The 20 mL of the aqueous solution containing 1 MBq of 211At
with respective pH was prepared by mixing of the pH adjusted aqueous solution and the 211At
stock solution in a 100-mL beaker. The dispersed 211At from the aqueous solution was collected
for 1h. The collected 211At on the filters and parts of the apparatus were quantified from theradioactivity by measuring the characteristic X-ray (211Po Kα : 79 keV). The 211At dispersion
experiments were performed by changing pH of the solutions in the range of pH 1-13 using
100-mL beakers. The dispersal rates of 211At are 13±4-30±2%, and the values depend on pHof the solution. At pH 7, the dispersal rate is highest, but the rate is reduced to 1.14±0.04%
by addition of 1wt% ascorbic acid. Dependence of exposed surface area of the solution to the
air was also studied with changing a vessel from 100-mL beaker to 1.5 mL PP tube at pH 7.
In the conditions, the dispersal rate was reduced with decreasing the air exposed surface areaof the solution. The distribution of 211At to a glass filter and charcoal filters were investigated.
The mole ratio of 211At collected to the glass filter and charcoal filters is 0.23±0.100.43±0.05:0.39±0.04-0.62±0.30 at pH 1-13. In the present setup, all the dispersed 211At were
filtered. While 3.4±0.2% of 211At passed through the glass filters even when 10 of the glass
filters were stacked. Therefore, a charcoal filter is necessary to completely collect the dispersed
211
At.
In summary, the dispersed 211At from various pH aqueous solution were collected by combining
glass filter, charcoal filter, and charcoal cartridges. The dispersal rate of 211At was dependent
on pH and the air exposed surface area of the solution. The rate was reduced by addition of
ascorbic acid to the 211At solution at pH 7.

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2018-2019At project211

Studies on Synthesis and QC Test Methods for
Low Molecular Compounds Labeled with 211At
I
Targeted Alpha-particle Therapy Research Project

SHIRAKAMI, Yoshifumi;1* KANEDA-NAKASHIMA, Kazuko;1 WATABE, Tadashi;2
LIU, Yuwei;2 OOE, Kazuhiro;2 TOYOSHIMA, Atsushi;1 SHINOHARA, Atsushi;3
SHIMOSEGAWA, Eku;4 and HATAZAWA, Jun5
1 Institute for Radiation Sciences, Osaka University
2 Department of Tracer Kinetics and Nuclear Medicine, Graduate School of Medicine, Osaka University
3 Department of Chemistry, Graduate School of Science, Osaka University
4 Department of Molecular Imaging in Medicine, Graduate School of Medicine, Osaka University
5 Research Center for Nuclear Physics, Osaka University* yoshifumi_shirakami@irs.osaka-u.ac.jp

Introduction
A radionuclide emitting alpha particles, astatine-211(211At), is known as a potential candidate
for targeted alpha therapy (TAT). We studied on synthesis of small molecules labeled with 211At
and their QC test methods.
Methods
A target plate of bismuth-209 was irradiated by helium ions and 211At was produced by anuclear reaction of 209Bi(He,2n)211At. 211At was separated and purified by a dry-distillation
method from the target plate and corrected as an aqueous solution of 211At. Several oxidants
and reductants were mixed with the 211At-aq. solution in order to elucidate chemical propertiesof 211At in the aq. solution. Radiolabeling of amino acid analogs were conducted by mixing
the 211At-aq. solutions with tyrosine and borono-substituted amino acids in the presence ofoxidizing agents. The reaction mixtures were analyzed by TLC and HPLC.
Results and Discussion
211
At-NaAt was obtained in a high radiochemical purity (97.9%) by addition of ascorbic acid
(Fig. 1). The borono-substituted amino acids were efficiently labeled with 211At (RCY> 90%)in the presence of oxidants such as N-bromosuccinimide. While tyrosine was not able to labelwith 211At by a method commonly used for radioiodine labeling.

Figure 1. HPLC profile of 211At-NaAt. Column: Cosmosil
5C18 MS(150mm), Eluent: 20mmole/L Tetrabutylammonium
chloride/acetonitrile (7:3), Flow rate: 1mL/min[1] Watabe T, Kaneda K, Liu Y, Shirakami Y, et al., J. Nucl. Med. 2019; 60:1301-1307.

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2018-201918

At project211

Stable and periodic supply of purified
211
At samples for the research project on
development of targeted alpha therapy

I
Targeted Alpha-particle Therapy Research Project

TOYOSHIMA, Atsushi;1* OOE, Kazuhiro;1,2 TERAMOTO, Takahiro;1
NAGATA, Kojiro;1 KON, Yukiyoshi;1 ICHIMURA, Soichiro;3 OBATA, Honoka;3
KANDA, Akimitsu;3 NAKAGAWA, Sota;3 YOSHIMURA, Takashi;1
FUKUDA, Mitsuhiro;1,4 and SHINOHARA, Atsushi1,3
1 Institute for Radiation Sciences (IRS), Osaka University
2 Graduate School of Medicine, Osaka University
3 Graduate School of Science, Osaka University
4 Research Center for Nuclear Physics (RCNP), Osaka University* toyo@irs.osaka-u.ac.jp

In the IRS, a research project on “development of targeted alpha therapy (TAT)” using ashort-lived α-particle emitter 211At has been conducted as an enterprise cross-departmentallycollaborated with Graduate School of Science, Graduate School of Medicine, and RCNP of
Osaka University. Due to the properties of an α-particle of the high energy-deposition and theshort range, the TAT is expected to be innovative cancer therapy to be able to eradicate small,metastatic tumors with less damage on surrounding normal cells. However, it is essentiallymandated to synthesize 211At-labelled compounds (pharmaceuticals) which are well-designed
and perfectly tuned to highly accumulate in targeted organs and tumors because of the shortrange of the α particles. The designed 211At-labelled compounds are then to be explored for theirrealistic in-vivo distribution in model animals since anti-tumor effects by high accumulation
should be needed to proceed to a next non-clinical test prior to a clinical trial. Such developments
require a lot of “trial and error” processes to finalize novel 211At-labelled pharmaceuticals.
For the rapid developments, we organized a stable and periodic supply system of 211At toRadioisotope Research Center (RRC), Osaka University. One of the sources is the productionof 211At in the 209Bi(α, 2n) 211At reaction at the AVF cyclotron of RCNP by ourselves. At
the F-course, an automated irradiation apparatus for the 211At production is installed andmaintained. Second, based on the contract between RI Beam Factory (RIBF), RIKEN and the
IRS, we have obtained an irradiated Bi target containing approximately 200 MBq of 211At 1-2
times a month. Another source is Supply Platform of Short-lived Radioisotopes supported by
JSPS Grant-in-Aid for Scientific Research on Innovative Areas, Grant Number 16H06278.
Based on the approval of our research proposal by the Supply Platform, an irradiated Bi target
containing 211At has been provided from RIBF of RIKEN, National Institute of Radiological
Sciences (NIRS) of National Institutes for Quantum and Radiological Science and Technology(QST), and Takasaki Advanced Radiation Research Institute of QST in a total of several times
per half a year.
At RRC in Suita campus, we always received the Bi target in a transfer container and carriedout chemical purification of 211At by dry distillation. Depending on the size and shape of thedelivered Bi target, we used different-sized quarts-stills for the distillation. The purified 211At
was mainly recovered by 100 μL of distilled water which was often fractionated into several
aliquots according to a number and required radioactivity of colleagues (users). Although
we are still improving the separation techniques, at present, recovery efficiency after the
separation is 50-70% and the separation time is within 1 h. Results on the synthesis of 211Atpharmaceuticals and the animal tests using the 211At samples can be found in this report book.
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IRS ANNUAL REPORT

2018-2019At project211

Development and Evaluation of Astatine-211
Conjugated Anti-CD20 Monoclonal Antibody
I
Targeted Alpha-particle Therapy Research Project

KABAYAMA, Kazuya;1 KANEDA-NAKASHIMA, Kazuko;2
MANABE, Yoshiyuki;1 SHIMOYAMA, Atsushi;1 TOYOSHIMA, Atsushi;2
SHINOHARA, Atsushi;1,2 and FUKASE, Koichi1,2*
1 Department of Chemistry, Graduate School of Science, Osaka University
2 Division of Science, Institute for Radiation Sciences, Osaka University* koichi@chem.sci.osaka-u.ac.jp

The principal aim of this study was development of next-generation internal radiotherapy using
211
At conjugated with cancer targeting molecules.
First, we synthesized anti-CD20 antibody conjugated decaborane (B10H14) with polyethylene
glycol (PEG) linker (Figure 1).1 211At was produced by the cyclotron, and then quickly purified
and combined to decaborane conjugated antibody. Now we are getting this 211At combined
antibody in about 80% yield.
Next, we performed cytotoxicity evaluation of 211At and this antibody using Raji cells(B lymphocyte cell line derived with Burkitt’s Lymphoma). As a result, the time- andconcentration-dependent cell death were confirmed in both 211At and this antibody. In theimmediate future, we plan to examine that the same study with anti-HER2 antibody for breast
cancer, and in vivo study using some tumor-bearing animals.

Figure 1. Structure of anti-CD20 antibody conjugated decaborane with PEG linker[1] (a) D. S. Wilbur. et al. Bioconjugate Chem., 2007, 18, 1226.
(b) H. Nakamae. et al. Cancer Res., 2009, 69, 2408.
(c) D. S. Wilbur. et. al. Nuclear Medicine and Biology, 2010, 37, 167.
(d) D. S. Wilbur. et. al. Bioconjugate Chem., 2011, 22, 1089.
(e) D. S. Wilbur. et al. Bioconjugate Chem., 2012, 23, 409.

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2018-201920

At project

211

Adsorption Behavior of Volatile Astatine(At) Compounds Observed with Developed
Thermochromatograph Apparatus

I
Targeted Alpha-particle Therapy Research Project

ICHIMURA, Soichiro;1* TOYOSHIMA, Atsushi;2 OOE, Kazuhiro;2,3
TERAMOTO, Takahiro;2 NAGATA, Kojiro;2 OBATA, Honoka;1 KANDA, Akimitsu;1
NAKAGAWA, Sota;1 YOSHIMURA, Takashi;2 and SHINOHARA, Atsushi1,2
1 Graduate School of Science, Osaka University
2 Institute for Radiation Sciences (IRS), Osaka University
3 Graduate School of Medicine, Osaka University* ichimuras17@chem.sci.osaka-u.ac.jp

Recently, targeted alpha therapy (TAT) using a short-lived α-particle emitter 211At attracts
attention. At Osaka University, the TAT with 211At is being developed. For the developments,
211
At is always produced by an irradiation of α beam on a metallic Bi target leading to the209
Bi(α, 2n) 211At reaction. Then, chemical purification of 211At from the irradiated Bi target
is performed by dry distillation. However, because chemical properties of At are not wellunderstood, there is no information on what kinds of At compounds are produced in the dry
distillation. Analysis of the distilled At compounds may provide insights into optimizationof the dry distillation. In this study, therefore, we first developed a thermochromatographapparatus to analyze At compounds vaporized from a Bi target. Then, adsorption behavior ofvaporized At compounds was studied.
In Fig. 1, a schematic of the developed thermochromatograph apparatus is shown. A thin,metallic Bi target containing 211At irradiated at the RIKEN AVF cyclotron was set in the quartz
column and was heated upto 850°C using a tubular furnace with flowing a gas, of which amixed ratio between inert gas and oxygen gas is 1:0, 3:1, and 0:1, at a rate of 20 mL/min. The
thermo-chromatographic column part neighboring on the furnace had a temperature gradientfrom 200°C down to -100°C. Temperature resolution was ±10°C on average. After vaporizing,an X-ray from 211At was measured with a CdZnTe detector to determine its adsorption position.
Several peaks of At with different adsorption temperature were observed under the inert gas
conditions. This means that a few At compounds are vaporized from the Bi target. Under
the conditions with only oxygen gas, only one peak was found at 40±7°C. This peak wasalso observed under the inert gas conditions. It is, thus, considered that the At compounds
vaporized from the target reacts with oxygen to form this compound. The present results
suggest that a few At compounds are formed in the dry distillation and their ratios are strongly
dependent on the gas conditions.

Fig.1. Schematic of developed apparatus.

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IRS ANNUAL REPORT

2018-2019At project

211

Determination of Ionic Radius of Astatide (At-)
in Aqueous Solutions
I
Targeted Alpha-particle Therapy Research Project

OBATA, Honoka;1* OOE, Kazuhiro;2,3 TERAMOTO, Takahiro;2 YOSHIMURA, Takashi;2
TOYOSHIMA, Atsushi;2 and SHINOHARA, Atsushi1,2
1 Graduate School of Science, Osaka University
2 Institute for Radiation Sciences (IRS), Osaka University
3 Graduate School of Medicine, Osaka University* obatah18@chem.sci.osaka-u.ac.jp

Recently, targeted alpha therapy (TAT) has attracted a great deal of attention as in-vivo
treatment irradiating target malignant tissues with short-lived alpha-emitters. A halogen
radioisotope, 211At (T1/2=7.2 h) is a promising candidate for TAT because it can be produced
relatively easily from a Bi target using an accelerator. Besides, both synthetic methods andclinical results for compounds labeled with lighter radioactive halogens, which are widely usedin radiopharmaceuticals, can be referred for developing 211At-labeled compounds. However,At chemistry is yet to be revealed in detail due to the lack of its long-lived radioisotopes.
Although astatide (At-) was reported to exist in aqueous solutions as other halogen elements
forming halides [1], any of its chemical properties remain unclear. Therefore, in this work,
we determined an ionic radius of At- for the first time by high-performance anion-exchange
chromatography (HPAEC).
211

At was produced via the 209Bi(α, 2n)211At reaction and was separated from the Bi target by dry
distillation. At-samples were prepared in a basic solution without any reductants, in a weakly
basic solution containing Na2SO3 as a reductant, and in a neutral solution containing Na2SO3.
HPAEC analyses of At-samples were carried out using an eluent with the same solution
composition as an At-sample to avoid chemical changes of the At species originally existing inthe sample. Retention behavior of At in the solutions was compared to that of other halides (X-)
and halates (XO3-): X = Cl, Br, I. The ionic radius of At- was evaluated by the extrapolation fromthe relationship between ionic radii and retention times in X-.
An anionic species of At was observed as a single peak in each of the obtained chromatograms.
While elution orders of the halogen ions were Cl-, Br-, and I- for X-, and IO3-, BrO3-, and ClO3for XO3-, the At species was retained most strongly among the studied halogen ions. Thisretention behavior of At agreed with the expected behavior of At- and not with that of AtO3-.
Using the relationship between the retention times and the ionic radii for X-, a Pauling-typeionic radius of the At- species was evaluated to be 2.34 ± 0.02 Å. This experimental value is ingood agreement with a theoretical ionic-radius of At- [2]. In conclusion, the At species studied
in this work was unambiguously verified to be At-, and its ionic radius was experimentally
determined for the first time.

[1] Guo et al., Inorg. Chem. 57, 4926−4933 (2018).
[2] Real et al., J. Chem. Phys. 144, 124513, 1−12 (2016).

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2018-201922

At project211

Targeted Alpha Therapy Using At-211 NaAt for
the Refractory Differentiated Thyroid Cancer
I
Targeted Alpha-particle Therapy Research Project

WATABE, Tadashi;1,2* KANEDA-NAKASHIMA, Kazuko;2
LIU, Yuwei;1 SHIRAKAMI, Yoshifumi;2 OOE, Kazuhiro;1,2
TOYOSHIMA, Atsushi;2 SHIMOSEGAWA, Eku;1,2 FUKUDA, Mitsuhiro;3
SHINOHARA, Atsushi;2,4 and HATAZAWA, Jun2,3
1 Graduate School of Medicine, Osaka University
2 Institute for Radiation Sciences, Osaka University
3 Research Center for Nuclear Physics, Osaka University
4 Graduate School of Science, Osaka University* watabe@tracer.med.osaka-u.ac.jp

For many years, radioactive iodine which emits beta rays has been used for treatment of
thyroid cancer. However, some thyroid tumors become resistant to iodine treatment (“iodinerefractory”), and a breakthrough approach is needed. Many research groups have attempted
to determine new methods for treatment of iodine-refractory thyroid cancer; none have showncompelling results—until now.
We successfully manufactured sodium astatide ([211At]NaAt) injection, a radiopharmaceuticalwhich emits α-particle, using the accelerator at the Research Center for Nuclear Physics andfacilities of the National Institute of Radiological Sciences. When NaAt was administered
to a mouse model of differentiated thyroid cancer, a remarkable tumor regression effect was
confirmed. As NaAt therapy is a systemic treatment, it can be applied to advanced cancers
with multiple metastases, and will be a new treatment option for refractory thyroid cancer. We
started consulting with PMDA (Pharmaceuticals and Medical Devices Agency), and we arepreparing for a physician initiated clinical trial in Osaka University Hospital.
The article, “Enhancement of astatine-211 uptake via the sodium iodide symporter by theaddition of ascorbic acid in targeted alpha therapy of thyroid cancer,” was published in the
Journal of Nuclear Medicine at DOI: https://doi.org/10.2967/jnumed.118.222638.

Figure: Treatment effect after the administration of sodium astatidewith the distribution image of the xenograft mice.

23

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2018-2019

Ac project225

Supply of 225Ac Separated from 229Th Generator
to Develop Targeted Alpha Therapy
I
Targeted Alpha-particle Therapy Research Project

TOYOSHIMA, Atsushi;1* KIKUNAGA, Hidetoshi;2 SHIRASAKI, Kenji;3
NAGATA, Kojiro;1 and TSUKADA, Kazuaki4
1 Institute for Radiation Sciences, Osaka University
2 Research Center for Electron Photon Science, Tohoku University
3 Institute for Materials Research (IMR), Tohoku University
4 Advanced Science Research Center (ASRC), Japan Atomic Energy Agency (JAEA)* toyo@irs.osaka-u.ac.jp

In recent years, targeted alpha therapy (TAT) using a short-lived α-particle emitter attracts
attention since its high efficacy in cancer therapy has been demonstrated [1]. One of thepromising nuclides is 225Ac which has a 10-d half-life and emits 4 α-particles including its shortlived descendant nuclides before terminating into a stable 209Bi nuclide. Due to its moderately
long half-life, this radioisotope is anticipated to be a good probe suitably conjugated with suchas an antibody which has slow kinetics in a living body.
225

Ac can be produced only by either nuclear reactions using an accelerator or a decay of 229Th
via 225Ra. The latter is an easier way if possessing 229Th or its parent nuclide 233U. At both the
IMR and ASRC, purified 229Th sources with several hundred kBq each have stored. Althoughthese amounts are not sufficient to conduct clinical trials, primary experiments on 225Acpharmaceuticals synthesis and animal tests can be proceeded. Therefore, we started a supplyof 225Ac separated from the 229Th sources at IMR and ASRC. In this report, a typical procedure
applied to the 225Ac separation is presented.
A dry residue containing 229Th and its descendants was dissolved with 0.5 mL of 8 M HNO3 andwas loaded on 2 connected anion-exchange columns (Muromac 1×8, 100–200 mesh, NO3- form,
1-mL column). Then, 3 mL of 8 M HNO3 was loaded on the columns to elute 225Ra and 225Ac.
For only the bottom column, 3 mL of 8 M HNO3 was loaded to completely strip these nuclides.
229
Th on the top column was separately recovered with 10 mL of 2 M HCl and 5-mL Milli-Q
water. After the 8 M HNO3 effluent was diluted to 4 M, this was loaded on a column filledwith DGA branched resin (2-mL cartridge, Eichrom). After 225Ra was eluted with 6 mL of 4 M
HNO3, 225Ac was stripped with 10 mL of 0.05 M HNO3. After evaporation to dryness, 225Ac wasdissolved in 0.2 mL of 0.2 M ammonium acetate solution in a small Teflon tube. The purified
sample was transferred to Radioisotope Research Center of Osaka University in a few days.
The radioactivity of 225Ac was determined by γ-ray using a Ge detector detecting the γ-rays of
its descendants 221Fr and 213Bi in radioactive equilibrium. 229Th/225Ac is provided by the 233U
cooperation project between JAEA and the Inter-University Cooperative Research Program of
the IMR, Tohoku University (Proposal Nos. 19K0053 and 19K0210).

[1] C. Kratochwil et al., J. Nucl. Med. 57(12), 1941-1944 (2016).

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2018-201924

Ac project

225

Theranostics Targeting Fibroblast Activation
Protein: Cu-64 and Ac-225 labelled FAPI-04 in
Pancreatic Cancer

I
Targeted Alpha-particle Therapy Research Project

WATABE, Tadashi;1,2* LIU, Yuwei;1 KANEDA-NAKASHIMA, Kazuko;2
SHIRAKAMI, Yoshifumi;2 LINDNER, Thomas;3 OOE, Kazuhiro;1,2 TOYOSHIMA, Atsushi;2
NAGATA, Kojiro;2 SHIMOSEGAWA, Eku;1,2 HABERKORN, Uwe;3 KRATOCHWIL, Clemens;3
SHINOHARA, Atsushi;2,4 GIESEL, Frederik L.;2,3 and HATAZAWA, Jun2,5
1 Graduate School of Medicine, Osaka University
2 Institute for Radiation Sciences, Osaka University
3 University Hospital Heidelberg, Heidelberg, Germany
4 Graduate School of Science, Osaka University
5 Research Center for Nuclear Physics, Osaka University* watabe@tracer.med.osaka-u.ac.jp

Pancreatic cancer is one of the leading causes of cancer related deaths worldwide. Patientswith pancreatic cancer often receive chemotherapy or radiation therapy, which are not always
effective and can have toxic side effects. In a collaborative research between Osaka University
and the University of Heidelberg, we succeeded in developing a new alpha-therapeutic agent(actinium-labeled fibroblast activating protein inhibitor ([225Ac] FAPI-04)) targeting the cancer
stroma surrounding cancer cells. When [225Ac] FAPI-04 was administered to a mouse modelof pancreatic cancer, the drug selectively accumulates in tumors and suppresses the tumor
growth. The cancer stroma provides the environment necessary for the growth of cancer cells
and also serves as a barrier to prevent cancer cells from the delivery of anticancer agents. In the
future, it is expected to be a revolutionary treatment for intractable pancreatic cancer for whichconventional treatment does not work. The article was published in The Journal of Nuclear
Medicine at DOI: 10.2967/jnumed.119.233122.

Figure: Treatment effect after the administration of 225Ac FAPI 04
with the distribution image of the xenograft mice.

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IRS ANNUAL REPORT

2018-2019

Research Activity

II

IRS ANNUAL REPORT

2018-201926

Carcinogenicity and Genome Variation in
Descendant Mice after the Every Generational
Low Dose-rate Internal 137Cs Radiation Exposure(Fukushima and Chernobyl Simulation
Experiment)
NAKAJIMA, Hiroo*
Institute for Radiation Sciences, Osaka University* nakajima@irs.osaka-u.ac.jp

To investigate the transgenerational effects of chronic low dose-rate internal radiation exposure
after the Fukushima and Chernobyl nuclear power plant accident, every generations of mice
were maintained in the radioisotope facility of Osaka University with free access to drinking
water containing Cesium-137 (100 Bq/ml).
It was performed all mouse genome sequences of the mouse (0, 15, 20, 24th generations inA/J) to detect accumulated genomic mutations such as SNVs (Single-Nucleotide Variants)
and InDels (insertion-deletion) in not only exons but also introns and intergenic regions.
Because small genomic mutations could occur, be inherited, and accumulate in each successive
generation in non-coding genomic regions and have no effect on survival.

II
Research Activity

It was compared levels of accumulated base mutations between the offspring exposed tocontinuous low-dose radiation and control mice of the same generation that started from alittermate mouse.
There was tendency of increasing the SNVs and the InDels at exon, intron and intergenic
sites in whole genome sequencing comparing each generation. However, even with repeatedgenerations there was not a large difference in the total base mutation rate between theCesium-137 group and the control group.
And now, it is also doing experiments of the carcinogenicity, immunoresponse and estimatinginternal radiation dose per generation.
If the amount of intake is converted to drinking water in humans, 100 Bq/ml water would
equate to 100000 Bq/ℓ. There was almost no effect on the mouse DNA even when the mice
consumed water containing this volume of radiation for 24 continuous generations. Mice
have almost the same spontaneous mutation rate per generation, base substitution rate per
nucleotide per generation, and number of genes as humans. Therefore, this inbred mouse
experiment is considered to be effective as an experiment to predict basic biological effects inhumans.
This work was partly supported by JSPS and Research on the Health Effects of Radiation
organized by Ministry of the Environment, Japan.

27

IRS ANNUAL REPORT

2018-2019

Training Course of Handling Radioisotopes
for Medical Students
NAKAJIMA, Hiroo;* and FUJIWARA, Tomoko
Institute for Radiation Sciences, Osaka University* nakajima@irs.osaka-u.ac.jp

Osaka University School of Medicine offers practical experiment mainly on physiology for
third-grade students. As part of this, two basic training items, “safe handling of radioisotope(RI)” and “biological effects of radiation” are set up in the radiation biology (basic radiation
medicine). In this fiscal year, we conducted training mainly on safe handling of unsealed RI
from November 25 to December 20, 2019. The total number of enrolled students was 111.

Practical training on safe handling of RI
BasicsStudents learned the physical properties of RI. The 32P aqueous solution was appropriately
diluted in consideration of the half-life and measurement efficiency. Using this sample, thefollowing three tasks were performed by the GM counter:
1) Measurement of the maximum energy using aluminum absorption plates.
2) The relationship between the distance and the count.
3) Statistical variation of the count.

II
Research Activity

Application
Practical training was conducted to learn the method of contamination inspection using
simulated contaminated samples using 3H (weak β-rays nuclide), 32P (strong β-rays nuclide),and 51Cr (gamma-rays nuclide).
The above three nuclides of known concentrations were applied to a stainless steel plate anddried to obtain a sample, which was wiped off with smear filter papers, and measured with a
GM counter, a gamma counter and a liquid scintillation counter.
In addition to understanding the measurement and wiping efficiencies, students learned
about the selection of measuring instruments based on nuclides, the safe handling of
unsealed RI, the treatment of wastes, and the significance of controlled areas.

Biological effects of radiation
The number of thymus and spleen cells after 24 hours in mice irradiated with X-rays (0, 1, 2, 4,
8 Gy) was counted to quantitatively examine the dose-dependent biological effects of radiation.

IRS ANNUAL REPORT

2018-201928

Fine Structural Analysis of Surface
with Electron Diffraction
OKADA, Michio*
Institute for Radiation Sciences, Osaka University* okada@chem.sci.osaka-u.ac.jp

Industrially relevant catalytically active surfaces exhibit defects. These defects serve as active
sites; expose incoming adsorbates to both high and low coordinated surface atoms; determine
morphology, reactivity, energetics, and surface relaxation. These, in turn, affect crystal
growth, oxidation, catalysis, and corrosion. Systematic experimental analyses of such surface
defects pose challenges, esp., when they do not exhibit order. High Miller index surfaces canprovide access to these features and information, albeit indirectly. We demonstrated that withquantitative low-energy electron diffraction (QLEED) intensity analyses and density functional
theory (DFT) calculations, we can visualize the local atomic configuration, the corresponding
electron distribution, and local reactivity [1]. The QLEED-determined Cu(410) structure(Pendry reliability factor RP ≃ 0.0797) exhibits alternating sequences of expansion (+) andcontraction (−) (of the first 16 atomic interlayers) relative to the bulk-truncated interlayer
spacing of ca. 0.437 Å. The corresponding electron distribution shows smoothening relative tothe bulk- determined structure, as shown in Fig. 1. These results should aid us to further gain
an atomic-scale understanding of the nature of defects in materials.

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Research Activity

Fig.1. Charge distributions of the BULK-truncated, DFT-optimized,
and QLEED-determined structures[1] R. Ahmed, T. Makino, J. S. Gueriba, S. Mizuno, W.A. Dino, M. Okada, Scientific Reports, 9, 16882 (2019)29

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Development of the New Radiation Monitoring
System Using DNA as a Radiation Sensor
SHIMIZU, Kikuo;1,3* MATUO, Youichirou;2 YAMAGUCHI, Miyabi;2 and IZUMI, Yoshinobu2,3
1 Radioisotope Research Center, Institute for Radiation Sciences, Osaka University, Toyonaka, Japan
2 Nuclear Power and Energy Safety Engineering, University of Fukui, Fukui, Japan
3 Institute of Nuclear Engineering, University of Fukui, Tsuruga, Japan* shimizu@rirc.osaka-u.ac.jp

We are developing a tissue-equivalent dosimeter comprised of DNA fragments using qPCR
technique. Real-time PCR selectively amplifies only a specific DNA fragment from a very small
amount of DNA solution and evaluating the initial amount of template DNA. The principleof the present method is that the amplification rate by the polymerase chain reaction is
proportional to the amount of template DNA in the sample, allowing evaluation of the quantityof damaged DNA by measuring the quantity of amplifiable undamaged template DNA.
The DNA fragments for ion beam irradiation were prepared using conventional PCR(amplification of 804 base pairs of URA3 gene). The amplified DNA fragments dissolved in TE
buffer (Tris-HCl 10 mM, EDTA 1 mM, pH7.4) were dropped on a sample plate and air dried.
The DNA sample was irradiated with carbon ions (LET: 55 keV/μm, at HIMAC and LET: 107
keV /μm at TIARA) and neon ions (LET: 335 keV/μm, at TIARA) with the dose of 0.01 - 10 Gy.
For comparison purpose, the DNA samples were also irradiated with the Gamma-ray (FromCo-60, LET 0.2 keV/μm at Osaka Univ). Real-time PCR was employed to amplify a 210-bp
region of the URA3 gene (related to nucleic acid metabolism) by using Real-Time PCR System(MJ Mini, Bio-Rad). SYBR green (SIGMA) was used to monitor the DNA amplification. The
obtained data were analyzed by the software “CFX Manager” (Bio-Rad) to calculate the relative
amount of DNA products in different samples. The ratio of replicable DNA decreased alongwith increasing dose in all type radiations, gamma-ray, carbon and neon ion beams. The effecton the reduction of replicable DNA was higher in the order of gamma-ray C ion and Ne ion.
This suggested that different types of lesions were produced per unit dose, depending on the
LET and affluence of ion beams. These results suggest that this method can be used to evaluate
the biological effects caused by various types of radiation with different LET. Furthermore, wewere able to evaluate the amount of DNA strand breaks by PCR using DNA extracted frombovine blood irradiated with gamma rays. We purified DNA from 2.0 ml of Bovine whole bloodusing QIAGEN’s Tissue kit. This result for this small amount sample suggests that this method
can be used for practical emergency exposure monitoring.

2018-2019

Research Activity

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Anion-exchange Experiment of Superheavy
Element, Dubnium, Together with its Homologs
Nb and Ta and Pseudo-homolog Pa
TOYOSHIMA, Atsushi;1* ADACHI, Sadia;2 TSUKADA, Kazuaki;3 KATO, Mizuho;4
KASHIHARA, Ayuna;2 ASAI, Masato;3 HABA, Hiromitsu;5 KOMORI, Yukiko;5
YOKOKITA, Takuya;5 SHIGEKAWA, Yudai;5 MORI, Daiki;5 WANG, Yang;5
NAKAJIMA, Akihisa;4 SUZUKI, Yusuke;4 NISHIZUKA, Kaito;4
TOKOI, Katsuyuki;6 and SUEKI, Keisuke4
1 Institute for Radiation Sciences, Osaka University
2 Graduate School of Pure and Applied Sciences, University of Tsukuba
3 Advanced Science Research Center, Japan Atomic Energy Agency
4 School of Science and Engineering, University of Tsukuba
5 Nishina Center for Accelerator-Based Science, RIKEN
6 Graduate School of Science and Engineering, Ibaraki University* toyo@irs.osaka-u.ac.jp

Superheavy elements (SHEs) with atomic number ≥ 104 are placed at the 7th period of the
Periodic Table of Elements. Due to increasingly strong relativistic effects, largely different
chemical properties from a trend in lighter homologs are theoretically expected for SHEs.
However, because of the difficulties of chemical experiments by extremely short half-lives (T1/2)
and low production rates in nuclear reactions, most of their chemical properties have not been
yet clarified. In our previous study on a group-5 SHE, dubnium (Db), its adsorption on anionexchange resin in 0.31 M HF/0.1 M HNO3 solution was found to be clearly weaker than that of
Ta and was similar to that of Nb and Pa [1]. This is very interesting because, based on a simple
anticipation from the periodicity, properties of Db should be similar to those of the closest
homolog Ta. Therefore, we started anion-exchange studies of Db in higher HF concentrations([HF]) where Nb and Pa show different behavior. In this report, we present results on on-line
anion-exchange experiments of Nb, Ta, and Db with a rapid chemistry apparatus (ARCA) at
RIKEN.

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Research Activity

Short-lived nuclides, 88gNb (T1/2 = 14.5 min), 170Ta (6.7 min), and 262Db (34 s), were producedin the natGe(19F, nx), natGd(19F, nx), and 248Cm(19F, 5n) reactions, respectively, using the RIKEN
AVF cyclotron. Reaction products transported by a He/KCl gas-jet were deposited in ARCA.
Then, elution behavior of these from an anion-exchange micro-column were studied with 0.114.5 M HF/ 1.0 M HNO3. For Db, behavior only in 14.5 M HF/ 1.0 M HNO3 was investigated.
Behavior of Nb and Ta was qualitatively consistent with results in batch experiments carriedout separately; adsorption of Ta was strong in a whole [HF] range, while Nb had a sudden
increase in adsorption beyond [HF] = 6 M. Pa had much weaker adsorption on the resin. In
14.5 M HF/ 1.0 M HNO3, where Nb and Ta strongly adsorb on the resin, while Pa has noadsorption, anion-exchange experiments of Db using ARCA have been successfully performed.
Data of Db are under analysis.

[1] Y. Kasamatsu et al., Chem. Lett. 38, 1084 (2009).
31

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2018-2019Synthesis and Properties of Thiohalidecapped
Hexanuclear Technetium Complexes
YOSHIMURA, Takashi;1,2* NAGATA, Kojiro;1 KINO, Yasushi;3 TAKAYAMA, Tsutomu;4
SEKINE, Tsutomu;5 and SHINOHARA, Atsushi1,2
1 Institute for Radiation Sciences, Osaka University
2 Graduate School of Science, Osaka University
3 Graduate School of Science, Tohoku University
4 Department of Chemistry, Daido University
5 Institute for Excellence in Higher Education, Tohoku University* tyoshi@rirc.osaka-u.ac.jp

The octahedral hexanuclear technetium(III) complexes is interesting to systematicallyinvestigate the influence of metal ions on the physical and chemical properties of the complexes.
We report the synthesis, structures, and spectroscopic and electrochemical properties of thethiohalide capped hexanuclear technetium complexes, [Tc6(μ3-S)8−n(μ3-X)nX6]n−4 (X = Br, n = 1, 2;
X = Cl, n = 1).1)
The high temperature reaction was applied to synthesize the thiohalide capped hexanuclear
technetium complexes. In the single-crystal X-ray analysis, the capping Br/S or Cl/S ligands
are disordered in the crystals and bromides occupy at all six terminal positions from theoccupancy analysis. A linear correlation is interestingly obtained for the plot of the bonddistances of Tc–S/Br as function of the occupancies of the capping bromides. In addition, theplot of M−Br terminal distances against the n value for [M6(μ3-S)8−n(μ3-Br)nBr6]n−4 (M = Tc, Re)
gives a linear correlation.

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Research Activity

The redox potentials shift positively by substitution of capping sulfide to bromide in thetechnetium complexes, and the potentials are always more positive than those of the isotypicrhenium clusters. The highest occupied molecular orbital (HOMO) and lowest unoccupied
molecular orbital (LUMO) of the technetium complexes are stabilized in energy comparedwith those of the rhenium analogues, as determined by the DFT calculations. The energy
gap between HOMO) and LUMO) for the technetium complexes are considerably smaller
than those of the corresponding hexanuclear rhenium complexes. The HOMOs of [Tc 6(μ3S)7(μ3-X)X6]3− (X = Cl, Br) are {Tc6(μ3-S)7(μ3-X)}3+ centered orbitals, and the LUMOs are puretechnetium d orbitals. These are similar to those of the hexanuclear rhenium analogues. In
contrast, the HOMO of [Tc6(μ3-S)6(μ3-Br)2Br6]2− is composed of the terminal bromides andhexnuclear technetium core orbitals.

1) T. Yoshimura, K. Nagata, et al., Dalton Trans. 2019, 48, 14085.

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2018-201932

Anion-exchange of Zr, Hf, and Th in HNO3
with the Automated Extraction Apparatus:
toward the Chemical Study of Rf
KASAMATSU, Yoshitaka;1* WATANABE, Eisuke;1 YOKOKITA, Takuya;2 HAYAMI, Sho;1
TONAI, Katsuma;1 SHIGEKAWA, Yudai;2 HABA, Hiromitsu;2 and SHINOHARA, Atsushi1
1
2

Graduate School of Science, Osaka University
Nishina Center for Accelerator-Based Science, RIKEN* kasa@chem.sci.osaka-u.ac.jp

The chemical properties of superheavy elements (SHEs) with atomic numbers of larger than
103 are expected to be characteristic among the homologues in the periodic table because ofstrong relativistic effects on their orbital electrons. For chemical experiments on short-lived
SHEs, new methods and apparatuses specialized for SHEs are needed. In our previous work,
the automated batch-type solid-liquid extraction apparatus (AMBER) was developed [1] andthe anion-exchange behavior of element 104, Rf, in HCl and H2SO4 was investigated. Towardfurther systematic experimental studies on Rf, in this study, we investigated the formationof the nitrate complexes of Zr, Hf, and Th (homologues of Rf ) and determined the suitable
experimental conditions for Rf experiments.

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Research Activity

We investigated the anion-exchange behaviors of Zr, Hf, and Th in HNO3 using Adogen 464
resin and 88Zr, 175Hf, and 234Th tracers by batch method. Then, the anion-exchange experiments
using AMBER were performed to determine the experimental conditions for washing of theresin and its repetitive use.
We determined the Kd values in anion exchange and the clear difference between complexationof Th (pseudo homologue of Rf ) and those of Zr and Hf was observed. The high Kd values of
Th indicates the formation of the anionic complexes, while the Kd values of Zr and Hf werevery low. In addition, it was found that anion-exchange reactions using Adogen 464 resin in
HNO3 rapidly reach the chemical equilibrium within 60 s of the shaking, which suggests that
this resin is promising for 261Rf (T1/2 = 68 s) experiments. It was also found that the Kd values
can be correctly obtained using AMBER for Zr, Hf, and Th in HNO3. When using 0.1 M HCl
for washing out of Zr, Hf, and Th adsorbed on the resin, 3 or 4 times of washing are sufficient,whereas 9 or 10 times are required for 0.1 M HNO3. Using the 0.1 M HCl washing solution,
100 times of repetitive anion-exchange experiments were achieved using AMBER. The constant
Kd values were obtained for 234Th. This result indicates that the Adogen 464 resin has sufficientdurability to conduct the repetitive anion-exchange experiment of 261Rf in HNO3. In conclusion,
the suitable experimental conditions using AMBER for anion exchange of Rf in HNO3 were
determined.

[1] Y. Kasamatsu, et al., Radiochim. Acta 103, 513 (2015).
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Maintenance of Chromosomal DNA
in Eukaryotic Cells
OKITA, Akiko K.;1,2 and NAKAGAWA, Takuro1*
1 Department of Biological Sciences, Graduate School of Biology, Osaka University, Japan
2 Present address: IFOM–The FIRC Institute of Molecular Oncology, Italy* takuro4@bio.sci.osaka-u.ac.jp

In eukaryotes, DNA is lapping around histone octamers, forming nucleosomes. Various kindsof modification of histones affect chromatin structure. Heterochromatin is highly condensed
chromatin structure and is characterized by di- and tri-methylation of 9th lysine of histone
H3. In contrast to euchromatin, heterochromatin blocks RNA polymerase transcription.
Although heterochromatin is known to be important for maintaining genome integrity andreducing the risk of cancer, it is still unclear how heterochromatin prevents gross chromosomal
rearrangements.
We used the fission yeast S. pombe as a model organism and found that heterochromatin
prevents gross chromosomal rearrangements at centromeres through the suppression oftranscription, especially Tfs1/TFIIS- and Ubp3/USP10-dependent transcriptional restartthat occurs after backtracking of RNA polymerases (Okita et al., 2019; Nakagawa and Okita2019). To determine the effect of Tfs1 on centromeric transcription, we performed Northernblot analysis. 10 µg of total RNAs prepared from yeast cells was suspended in MOPS buffer(20mM MOPS pH 7.0, 2 mM NaAc, 1 mM EDTA) supplemented with 8% formaldehyde,
50% deionized formamide, and 10 μg/ml ethidium bromide and heated at 55 °C for 60 min.
RNAs were resolved by 1.0% PrimeGel agarose LE (TaKaRa) gel electrophoresis in MOPS
buffer supplemented with 2.2M formaldehyde. After soaking the gel in 50mM NaOH for 20
min, RNAs were transferred to a 0.45 μm ClearTrans nylon membrane by capillary action inalkaline transfer buffer (10 mM NaOH, 3M NaCl) and covalently attached to the membrane by
150 mJ UV irradiation. Radioactive DNA probes prepared using α-32P-dCTP (PerkinElmer Life
Sciences) and Random primer labeling kit ver. 2 (Takara) were used to detect of specific RNAs.
Radioactive signals were detected using BAS2500 phosphorimager (Fuji Film). Our results
show that loss of Tfs1 reduces centromeric RNAs as well as the rate of gross chromosomal
rearrangements in heterochromatin-deficient cells. These studies implicate Tfs1- and Ubp3transcription in gross chromosomal rearrangements.

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Research Activity

Okita AK, Zafar F, Su J, Weerasekara D, Kajitani T, Takahashi TS, Kimura H, Murakami Y, Masukata H, Nakagawa T. (2019)
Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependenttranscription. Commun Biol 2, 17.
Nakagawa T, Okita AK (2019) Transcriptional silencing of centromere repeats by heterochromatin safeguards chromosome
integrity. Curr Genet 65(5), 1089-1098.

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2018-201934

Performance Study on new Front-end ASIC
of Pixel Detector for High-Luminosity Upgradeof the ATLAS experiment
HIROSE, Minoru;* and NANJO, Hajime#
Graduate School of Science, Osaka University* hirose@champ.hep.sci.osaka-u.ac.jp#
nanjo@champ.hep.sci.osaka-u.ac.jp

We are searching for new physics beyond the standard model of particle physics with the
ATLAS detector at the Large Hadron Collider (LHC). The LHC will be upgraded to havehigher luminosity of the proton beam (HL-LHC) in 2025-2027. The ATLAS detector will be
upgraded for the HL-LHC. We are preparing new silicon pixel sensors with better radiation
hardness and more granular pixel size (50μm × 50μm), which will be installed for tracking
charged particles near the collision point. A new front-end circuit with high-speed data rate
is required on the sensor due to the higher luminosity and the expected higher trigger rate.
The circuit is 2-cm square with the pixel structure of 50 μm × 50 μm to receive signal from thecorresponding sensor pixel. The circuit is designed as an ASIC and is attached to the sensor.
Signal charge is generated from the particle hit in the sensor, and the signal is amplified anddigitized at the front-end circuit with a charge threshold set for each pixel. The digital datais transferred through four lanes with the data rate of 1.28 Gbps / lane. It is handled with adownstream electronics, and is stored in a computer. Prototype ASICs (Fig. 1) of 2 cm × 1 cm
size were developed recently for the front-end circuit.

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Research Activity

We need to tune the charge thresholds for all the pixels in order to have uniform signal
efficiency. The threshold is set with digital values via digital communication to the ASIC, andthe digital values can be converted to the charges by injecting test pulses with known amountsof the charge. Osaka members developed new algorithm to tune the charge thresholds, andhave shown that more than 99.7% of all the pixels can be tuned properly.
We should have a test system for the high-speed data output of the ASICs. A circuit with a
Field Programable Gate Array (FPGA) is used to receive data from the ASIC and store it to
a computer. Osaka members developed circuits and a test system to handle such high speed
data. Our members developed an interface printed circuit board (Fig. 2) between the ASIC
and the FPGA circuit, and have shown that the interface board can handle high speed data
up to 3 Gbps / lane. Our members also developed the FPGA firmware, and have succeeded tohandle 1.28 Gbps / lane with the firmware. Osaka group is responsible for such crucial items,
and provided the interface board and the firmware to the ATLAS community as a common test
system.

Fig.1: Front-end circuit (ASIC)

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2018-2019

Fig. 2: Interface board

Identification of 90Sr and Plutonium Isotopes
from the Radioactive Particles Released fromthe Accident of FDNPPNINOMIYA, Kazuhiko;1,2* IGARASHI, Junya;1 ZHANG, Zijian;1 KAJIWARA, Tomohiro;1
MATSUDA, Masaya;1 YAMAGUCHI, Yoshiaki;2 and SHINOHARA, Atsushi1,2
12Graduate School of Science, Osaka University
Radioisotope Research Center, Institute for Radiation Sciences, Osaka University* ninokazu@chem.sci.osaka-u.ac.jp

On March 11, 2011, large amount of radioactive nuclides were released into the environmentby the accident of Fukushima Dai-ichi Nuclear Power Plant. The detail process in the reactor
at the accident is strongly desired. In present, most of the radioactive nuclides were decay out
and long-lived radioactive nuclides such as 137Cs, 90Sr and 239Pu becomes important. By thedifferences on their chemical properties, the release behavior of these nuclides were different.
By investigating the amount and distribution of these nuclides, the progress and circumstancein the reactor at the accident can be clarified.

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Research Activity

In the FDNPP accident, micro-meter scale radioactive particles which were insoluble inwater and containing highly concentrated radioactive Cs were reported [1]. Because of its
high specific radioactivity, the radioactive particles are estimated to be formed in the reactor
during the meltdown and were directly released from the reactor. Due to its stability in theenvironment, the radioactive particles kept their elemental composition still now and retained
the original property at the time of emission from the reactor. In other words, the radioactive
particles are free from the environmental contamination. In this study, to investigate theformation process of radioactive particles, that is, the accident circumstance in the reactor
at the accident, we identified 90Sr and Pu isotopes (239Pu, 240Pu and 241Pu) in the radioactive
particles.
We found some radioactive particles near the FDNPP. Radioactivity of 137Cs for each radioactive
particle was determined from gamma-ray measurement by HPGe detector [2]. We performed
radiochemical analysis for the radioactive particles for separation of Sr and Pu, after that,
we identified 90Sr by low-background liquid scintillation
counter and Pu isotopes by inductively coupled plasmamass spectroscopy (ICP-MS) measurement [3]. Figure 1
shows the SEM (scanning electron microscopy) image ofthe radioactive particles analyzed in this study. For thisparticle, 90Sr and 239+240Pu activities were 0.171 ± 0.010 Bq
and (1.70 ± 0.20) × 10-5 Bq respectively.
Figure 1: The SEM image of the radioactive
particles analyzed in this study.

[1] K. Adachi et al., Sci. Rep., 3 (2013) 2554
[2] Z. Zhang et al., Environ. Sci. Technol. 53, (2019) 5868-5876[3] J. Igarashi et al., Sci. Rep 9 (2019) 11807

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2018-201936

New Electromagnetic Calorimeterwith a Photon/Neutron Discrimination PowerNANJO, Hajime;* and YAMANAKA, Taku#
Graduate School of Science, Osaka University* nanjo@champ.hep.sci.osaka-u.ac.jp#
taku@champ.hep.sci.osaka-u.ac.jp

We have developed and constructed a novel electromagnetic calorimeter that can distinguishbetween neutrons and photons based on shower depths.
We are pursuing the KOTO experiment at J-PARC to search for new physics beyond theStandard Model by using the rare neutral kaon decay, KL → π0 νν, as a probe. The signatureof the decay is two photons from the π0 decay hitting an electromagnetic calorimeter with noother visible particles. The calorimeter is made of 2700 50-cm-long (27 radiation lengths)
CsI crystals stacked inside a 2-m-diameter cylinder. One of the major backgrounds to thisdecay is caused by neutrons traveling outside the beam hitting the calorimeter and producing
a secondary neutron. If the initial and secondary neutrons produce hadronic showers, theymight mimic electromagnetic showers by a π0 decay. We had rejected such events based on
shower shapes and pulse shapes, but we still needed another order of magnitude suppression.

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Research Activity

We came up with an idea to distinguish between photons and neutrons based on their shower
depths. The photon showers start near the upstream end of the crystals whereas neutron
showers start almost anywhere in the 50-cm-long crystal. This difference is caused by thedifference between the radiation length (1.9 cm) and the interaction length (38 cm) of CsI,
which determines the starting points of electromagnetic showers and hadronic showers,
respectively. To measure the shower depths, we decided to attach silicon photosensors (MPPC)on the upstream ends of the CsI crystals. The difference of propagation times for scintillation
light traveling towards upstream and downstream ends in the CsI crystal reflects the shower
depth.
Our group at Osaka has studied the neutron rejection power with Monte Carlo simulations, andseveral beam tests with electrons, photons, and neutrons. We have also developed a scheme toglue the MPPCs on CsI crystals, and electronics to operate the photosensors. In the fall of 2018,
we attached 4000 photosensors on 2700 CsI crystals. We then collected data with the upgradedcalorimeter. One of our graduate students analyzed the data to evaluate the neutron rejection
power with the new calorimeter. The figure below shows the timing difference between
signal observed by the MPPCs and phototubes. The π0 sample collected with KL → 3π0 decays
has a sharp peak whereas the enhanced
neutron background sample has a broader
distribution. By applying a cut to accept 90%of the π 0 sample, the neutron backgroundwas shown to be suppressed by a factor of 50
which was more than we originally planned.
With this upgraded calorimeter, the neutroninduced background is suppressed sufficiently
for now on.

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2018-2019

Current Interstitial Brachytherapy
for Tongue Cancer
MURAKAMI, Shumei;* IWAMOTO, Yuri; TSUJIMOTO, Tomomi; and MARUTANI, Keisuke
Department of Oral and Maxillofacial Radiology
Graduate School of Dentistry, Osaka University* shumei@dent.osaka-u.ac.jp

Oral cancer is a rare lesion in Japan, but more than 12,000 people are diagnosed as the oral
cancer per year and the number of these patients have been increasing. And, the tongue is mostdominant in all oral cancer sites and more than half. Although a main treatment modality forthe tongue cancer is surgery, the radiation therapy is also applied to preserve many functions
and configuration of the tongue.
The radiation therapy is classified into two groups, the external beam radiation therapy and thebrachytherapy using a small radioactive source. For the radical treatment of the tongue cancer,
the interstitial brachytherapy (ISBT) is often applied, because it is excellent in concentration of
the radiation dose.

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Research Activity

In our institute more than 300 patients with the tongue cancer have been treated by the highdose rate (HDR) ISBT with a remote after loading system (RALS), and the local control rates
are 92% in T1 (< 2 cm) cases and 84% in T2 (< 4 cm) cases. Although the treatment result issatisfactory, we have encountered some patients who had suffered from the osteoradionecrosisin the mandible as a late complication because of an excess absorbed dose in the mandible.

Recently, we invented a new radiation protection device to prevent the complications and haveapplied it to 50 patients. Until now the acute and late complications have not been observed.

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Estimation of Background Gamma-ray
Spectrum for High-precision Dosimeter for
Future Fukushima
MURATA, Isao;1* ANGXUAN, Jiang;1 TAMAKI, Shingo;1
KUSAKA, Sachie;1 and SATO, Fuminobu1
1

Graduate School of Engineering, Osaka University* murata@see.eng.osaka-u.ac.jp

1. Introduction
In Fukushima, decontamination is continuously carried out to make the activity level down toan acceptable level. In the present study, We focus on future Fukushima. Recently, the activity
level surely decreases by the decay and decontamination. However, it is not zero and the fear
may last forever. At present, the dose rate of 137Cs can be measured accurately by using a highprecision detector like a Ge detector. However, it is very expensive and time-consuming, andrequires expertise. We are thus developing a new high-precision dosimeter to show the 137Cs
dose separately and accurately, even if the dose is lower than the background level, because
we need to deliver accurate information to Fukushima people and they have a right to know it.
The high-precision dosimeter requires an accurate background spectrum at the place where
measurement is carried out, in order to estimate the 137Cs dose accurately. For this purpose, weplan to research via three stages. The first stage is to study the characteristics of background invarious places and the second stage is to predict the background contained in actually measured
gamma-ray spectra in stage 1. The third stage is to subtract the estimated background from theactually measured gamma-ray spectrum in Fukushima to estimate the dose of 137Cs accurately,even if the level is lower than the background.

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Research Activity

2. Background measurement experiment and spectrum analysis
In this study background spectra were measured in various places such as on the ground (onthe soil, on the asphalt), indoor (basement, concrete room), in the air, on the water and so on.
We analyzed the measured gamma-ray spectra to find out why it is so distributed. The specificcharacteristics of the gamma-ray spectrum of the background, i.e., energy, intensity, precursor
nuclide, decay chain and so on, are being analyzed to find out measuring-position dependenceof the background spectrum shape. From the result, the peaks consist of 40K, uranium series
and thorium series.
3. Verification experiments and the evaluation by Bayes estimation method
The Bayes estimation method was applied to estimate the very low 137Cs dose in Fukushima,
because it is necessary to predict the contribution of background component in the measured
pulse height spectrum, which cannot be known in advance. Thereafter, background prediction
and detection limit verification experiments were performed. It was found to be feasible toestimate the corresponding background by using the Bayes estimation method even when
making short-time measurements.
4. Conclusion
In this research, a new technique was proposed to realize the background estimation fordevelopment of a new high-precision dosimeter for future Fukushima. In conclusion, thebackground can accurately be estimated by using the Bayes estimation method, and 137Cs dose
rates down to 0.00022 μSv / h can be measured in an acceptably high accuracy.
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Fabrication of Radiophotoluminescence
Dosimeter with 3D-printing Technology
SATO, Fuminobu;1* HASHIMOTO, Taichi;1 TAMAKI, Shingo;1
KUSAKA, Sachie;1 MIYAMARU, Hiroyuki;2 and MURATA, Isao1
12

Graduate School of Engineering, Osaka University
Radiation Research Center, Osaka Prefecture University* fsato@see.eng.osaka-u.ac.jp

Conventional dosimeters mostly comprise limited shapes, and generally based on point
measurements. For example, in the case of an individual dosimeter, the dose value of thechest or abdomen is evaluated as a representative value without identifying the exposed
part. However, in advanced radiotherapy systems and accelerator-type radiation generators
in recent years, the directional dependence of the radiation source is significant, and there
are many dosimeters of local radiation exposure in which specific parts are irradiated.
Therefore, it is increasingly important for radiation safety management to confirm theradiation-irradiated parts. Therefore, we developed three- dimensional (3D) dosimeters withradiophotoluminescence (RPL) material via fused-deposition modelling (FDM) 3D-printing
technology. The 3D RPL dosimeter was a composite material consisting of polycaprolactone(PCL) resin and RPL glass. The RPL glass dosimeter powder was mixed with the PCL resin
powder homogeneously. The mixture was put into a filament-manufacturing machine for
3D printer. RPL filaments were produced by extrusion through a discharge port at 70 °C.
The shape data for 3D dosimeters were designed by CAD software. Some 3D dosimeters
were printed out via FDM 3D-printing technology. Figure 1 shows an ear-shaped dosimeter
fabricated as a prototype. A surface of each dosimeter was irradiated with collimated X-ray
beam. By excitation of UV light, orange fluorescence was emitted from the X-ray irradiatedparts. Moreover, the irradiated-region of the 3D dosimeter could be confirmed with naked eye
over approximately 500 mGy. The RPL photographs of the 3D dosimeters were obtained andanalyzed to evaluate the dose profiles through digital image processing. Although there aresome problems, the phantom printed out with 3D printer will be one of candidates of a newphantom for evaluating the radiation exposure of human body.

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Research Activity

Figure 1. Photograph of ear-shaped dosimeter irradiated by X-ray beam. The absorbed dose wasapproximately 30Gy. (a) Photograph under white LED lighting. (b) RPL photograph shows that theirradiation part is clearly observed. (c) Dose profile obtained by the analysis of the RPL photograph (b).

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2018-201940

Irradiation Induced Amorphizationin High Entropy Alloys
NAGASE, Takeshi1,2*
12Research Center for Ultra-High Voltage Electron Microscopy, Osaka University
Graduate School of Engineering, Osaka University* t-nagase@uhvem.osaka-u.ac.jp

A new generation of structural and functional materials are urgently required to meet the
Sustainable Development Goals (SDGs). Recently, a new class of structural materials called
high-entropy alloys (HEAs) was developed. HEAs were recognized as the multicomponent
alloys whose mixing entropy was over 1.5 R (R is gas constant). The occurrence of solid state
amorphization (SSA) in AlTi0.5ZrCuNiPd HEA was observed by in situ transmission electron
microscopy (TEM) under MeV fast electron irradiation via high voltage electron microscopy(HVEM) [1]. Body-centered-cubic (BCC) single phase specimens can be obtained via thesolidification of the thermal melt with the appropriate cooling rate in AlTi0.5ZrCuNiPd HEA.
Figure 1 shows the typical example of the in-situ TEM observation in AlTi0.5ZrCuNiPd HEA[1]. In BF images, featureless contrast appeared at the central region of the irradiation. In SAD
patterns shown as the inset at upper right side, broad halo rings appeared together with thedisappearance of the diffraction spots corresponding to BCC crystalline phase. This is the firstexperimental evidences for the occurrence of SSA in HEAs under MeV electron irradiation.

II
Research Activity

Figure 1. In situ TEM observation of SSA behavior in HEA using Hitachi H-3000 ultra-high voltage
electron microscope installed at Osaka University [1].

[1] T. Nagase, A. Takeuchi, K. Amiya, T. Egami, Materials Chemistry and Physics, 210, 291-300 (2018).,“Solid State Amorphization of Metastable Al0.5TiZrPdCuNi High Entropy Alloy Investigated by High Voltage Electron
Microscopy”,
http://doi.org/10.1016/j.matchemphys.2017.07.071
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Achievements

III

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2018-201942

Original Paper
O-1

Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel
therapeutic drug for AML with high EVI1 expression
Hasi Rani Saha, Kazuko Kaneda-Nakashima, Shunsuke Shimosaki, Akira Suekane, Bidhan Sarkar, Yusuke Saito,
Honami Ogoh, Shingo Nakahata, Kentaro Inoue, Takayoshi Watanabe, Hiroki Nagase, Kazuhiro Morishita
Scientific reports, 2018, 8, 13741.

O-2

Study of Mutation from DNA to Biological Evolution

Bando Masako, Kinugawa Tetsuhiro, Manabe Yuichiro, Masugi-Tokita Miwako, Nakajima Hiroo, Suzuki, Kazuyo,
Tsunoyama Yuichi, Wada Takahiro, Toki Hiroshi
Int. J. Radiat Biol. Int. J. Radiat Biol., 2019, 20, 1.
O-3

Verification of a dose rate-responsive dynamic equilibrium modelon radiation-induced mutation frequencies in mice

Yuichi Tsunoyama, Kazuyo Suzuki, Miwako Masugi-Tokita, Hiroo Nakajima, Yuichiro Manabe, Takahiro Wada,
Masako BandoInt. J. Radiat Biol. Int. J. Radiat Biol., 2019, 95, 1414.
O-4

放射線誘発変異発生頻度線量率応答モデル WAM モデルを用いた
ラッセルのマウス実験結果の再解析

角山雄一 , 鈴木和代 , 馬杉美和子 , 中島裕夫 , 真鍋勇一郎 , 和田隆宏 , 坂東昌子
日本放射線安全管理学会誌 , 2018, 17, 138.

O-5

マウスを用いたセシウム 137 の慢性的低線量内部被ばくによる成体と子孫への影響の定量的実験検証

中島裕夫 , 大野みずき , 石原弘
環境省原子力災害影響調査等事業（放射線の健康影響に係る研究調査事業）放射線による健康影響の解明及び放射線以外の要因による健康リスクの低減を含めた総合的な健康リスクに関する研究 , 2018, 63

O-6

Quantitative Multilayer Cu(410) Structure and Relaxation Determined by QLEED
Rezwan Ahmed, Takamasa Makino, Jessiel Siaron Gueriba, Seigi Mizuno, Wilson Agerico Diño, Michio Okada
Scientific Reports, 2019, 9, 16882.

O-7

CH3Cl/Cu(410): Interaction and Adsorption Geometry

Takamasa Makino, Siti Zulaehah, Jessiel Siaron Gueriba, Wilson Agerico Diño, Michio Okada
J. Phys. Chem. C, 2018, 122, 11825.
O-8

Adsorption geometry of methyl chloride interacting weakly with Ag(111)
Kotaro Takeyasu, Michio Okada
J. Phys. Comm., 2018, 2, 75017.

O-9

超音速分子ビームによる表面化学反応研究

岡田美智雄
生産と技術 , 2019, 71, 66.

III

O-10

Achievements

Biological effects of carbon ion beams with various LETs in budding yeast
Saccharomyces cerevisiae
Youichirou Matuo, Yoshinobu Izumi, Yoshiya Furusawa, Kikuo Shimizu
Mutant. Res., 2018, 810, 45.

O-11

Molecular Analysis of Carbon Ion Induced Mutations
in DNA repair deficient strains of Saccharomyces cerevisiae

Youichirou Matuo, Yoshinobu Izumi, Ayako N. Sakamoto , Yoshihiro Hase, Katsuya Satoh, Kikuo Shimizu
Quantum beam Sci., 2019, 3, 1
O-12

Extraction behavior of Mo and W from H2SO4 and HF/HCl solutions into toluene with
Aliquat336: sulfate and fluoride complex formation of Mo and W towards chemical
studies of seaborgium (Sg)Atsushi Toyoshima, Akina Mitsukai, Kazuaki Tsukada, Kazuhiro Ooe, Hiromitsu Haba, Yukiko Komori,
Masashi Murakami, Yusuke Kaneya, Daisuke Sato, Masato Asai, Tetsuya K. Sato, Yuichiro Nagame
J. Radioanal. Nucl. Chem., 2018, 317, 421.

O-13

First Ionization Potentials of Fm, Md, No, and Lr:
Verification of Filling-Up of 5f Electrons and Confirmation of the Actinide Series

Tetsuya K. Sato, Masato Asai, Anastasia Borschevsky, Randolf Beerwerth, Yusuke Kaneya, Hiroyuki Makii, Akina
Mitsukai, Yuichiro Nagame, Akihiko Osa, Atsushi Toyoshima, Kazuaki Tsukada, Minoru Sakama, Shinsaku Takeda,
Kazuhiro Ooe, Daisuke Sato, Yudai Shigekawa, Shin-ichi Ichikawa, Christoph E. Duellmann, Jessica Grund,Dennis Renisch, Jens V. Kratz,Matthias Schaedel, Ephraim Eliav,Uzi Kaldor, Stephan Fritzsche, Thierry Stora
J. Am. Chem. Soc., 2018, 140, 14609
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O-14

Electron-tracking Compton camera imaging of technetium-95m

Yuichi Hatsukawa, Takehito Hayakawa, Kazuaki Tsukada, Kazuyuki Hashimoto, Tetsuya Sato, Masato Asai,
Atsushi Toyoshima, Toru Tanimori, Shinya Sonoda, Shigeto Kabuki, Hiroyuki Kimura, Atsushi Takada,
Tetsuya Mizumoto, Seiya Takaki
PLOS one, 2018, 13, e0208909
O-15

Extraction behavior of rutherfordium as a cationic fluoride complex
with a TTA chelate extractant from HF/HNO3 acidic solutions

Akihiko Yokoyama, Yuta Kitayama, Yoshiki Fukuda, Hidetoshi Kikunaga, Masashi Murakami, Yukiko Komori,
Shinya Yano, Hiromitsu Haba, Kazuaki Tsukada, Atsushi Toyoshima
Radiochim. Acta, 2018, 107, 27.
O-16

Formation and thermochemical properties of oxychlorides of niobium (Nb) andtantalum (Ta): Towards the gas-phase investigation of dubnium (Db) oxychloride
Nadine M. Chiera, Tetsuya K. Sato, Tomohiro Tomitsuka, Masato Asai, Hayato Suzuki, Katsuyuki Tokoi,
Atsushi Toyoshima, Kazuaki Tsukada, Yuichiro Nagame
Inorg. Chim. Acta, 2019, 486, 361.

O-17

Radiotheranostics Coupled between an At-211-Labeled RGD Peptide
and the Corresponding Radioiodine-Labeled RGD Peptide

Kazuma Ogawa, Takuya Takeda, Kenji Mishiro, Atsushi Toyoshima, Kazuhiro Shiba, Takashi Yoshimura,
Atsushi Shinohara, Seigo Kinuya, Akira OdaniACS Omega, 2019, 4, 4584.
O-18

Optimization of an isothermal gas-chromatographic setup
for the chemical exploration of dubnium (Db, Z=105) oxychlorides

Nadine M. Chiera, Tetsuya K. Sato, Tomohiro Tomitsuka, Masato Asai, Yuta Ito, Kaori Shirai, Hayato Suzuki,
Katsuyuki Tokoi, Atsushi Toyoshima, Kazuaki Tsukada, Yuichiro Nagame
J. Radioanal. Nucl. Chem., 2019, 320, 633.
O-19

Dispersal rates of astatine-211 from aqueous solutions and chloroform

Atsushi Toyoshima, Kojiro Nagata, Kazuhiro Ooe, Zijian Zhang, Takumi Ikeda, Soichiro Ichimura, Honoka Obata,Takashi Yoshimura, Atsushi Shinohara
Radiation Safety Management, 2019, 18, 16.
O-20

Synthesis and Photoluminescence of Tetracyanidonitridorhenium(V) Complexes
with Five-Membered N-Heteroaromatic Ligands
and Photoluminescence-Intensity Change
Moe Seike, Kojiro Nagata, Hayato Ikeda, Akitaka Ito, Eri Sakuda, Noboru Kitamura, Atsushi Shinohara,
Takashi YoshimuraACS Omega, 2019, 4, 21251.

O-21

Synthesis, structures, redox properties, and theoretical calculations of thiohalide
capped octahedral hexanuclear technetium(III) clusters

III

O-22

Achievements

Takashi Yoshimura, Kojiro Nagata, Ayumi Matsuda, Tishiki Omote, Yasushi Kino, Tsutomu Takayama,
Tsutomu Sekine, Atsushi Shinohara
Dalton Transactions, 2019, 48, 14085.

A luminescent dicyanidonitridotechnetium(v) corewith tridentate ligand coordination sites

Takashi Yoshimura, Kojiro Nagata, Tatsuki Shiroyama, Yasushi Kino, Tsutomu Takayama, Tsutomu Sekine,
Atsushi Shinohara
Dalton Transactions, 2018, 47, 16027.
O-23

健全な放射線防護実現のためのアイソトープ総合センターをベースとした
放射線教育と安全管理ネットワークの紹介

吉村崇
日本放射線安全管理学会誌 , 2018, 17, 77.

O-24

Amino Acid Selective C-13 Labeling and C-13 Scrambling Profile Analysis
of Protein alpha and Side-Chain Carbons in Escherichia coli Utilized
for Protein Nuclear Magnetic ResonanceToshihiko Sugiki, Kyoko Furuita, Toshimichi Fujiwara, Chojiro Kojima
Biochemistry, 2018, 57, 3576.

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44

O-25

Phosphoinositide binding by the PH domain in ceramide transfer protein (CERT) is
inhibited by hyperphosphorylation of an adjacent serine-repeat motif

Toshihiko Sugiki, Daichi Egawa, Keigo Kumagai, Chojiro Kojima, Toshimichi Fujiwara, Koh Takeuchi, Ichio Shimada,
Kentaro Hanada, Hideo Takahashi
The Journal of biological chemistry, 2018, 293, 11206.
O-26

Absolute H-1 polarization measurement with a spin-correlated component ofmagnetization by hyperpolarized MAS-DNP solid-state NMR
Toshimichi Fujiwara
Solid State Nuclear Magnetic Resonance, 2019, 99, 20.

O-27

The Route from the Folded to the Amyloid State:
Exploring the Potential Energy Surface of a Drug-Like Miniprotein

Nóra Taricska, Dániel Horváth, Dóra K. Menyhárd, Hanna Ákontz-Kiss, Masahiro Noji, Masatomo So, Yuji Goto,
Toshimichi Fujiwara, András Perczel
Chemistry-A Europian Journal, 2019, 26, 1968
O-28

Noise peak filtering in multi-dimensional NMR spectrausing convolutional neural networks

Kobayashi N, Hattori Y, Nagata T, Shinya S, Güntert P, Kojima C, Fujiwara T
Bioinformatics, 2018, 34, 4300.
O-29

Veratridine binding to a transmembrane helix of sodium channel Nav1.4 determinedby solid-state NMR
Niitsu A, Egawa A, Ikeda K, Tachibana K, Fujiwara T
Bioorganic & medicinal chemistry, 2018, 26, 5644.

O-30

Transient antibody-antigen interactions mediate the strain-specific recognitionof a conserved malaria epitope

Bankala Krishnarjuna, Toshihiko Sugiki, Rodrigo A, V. Morales, Jeffrey Seow, Toshimichi Fujiwara, Karyn L. Wilde,
Raymo, S. Norton, Christopher A. MacRaild
Communications Biology, 2018, 1, 58.
O-31

The relationship between dispositional empathy, psychological distress,
and posttraumatic stress responses among Japanese uniformed disaster workers:a cross-sectional study
Tanaka H, Akutsu H, Yabuta I, Hara M, Sugimoto H, Ikegami T, Watanabe T, Fujiwara T
BMC psychiatry, 2018, 18, 328.

O-32

A novel chitin-binding mode of the chitin-binding domain of chitinase A1
from Bacillus circulans WL-12 revealed by solid-state NMR.

Hiroki Tanaka, Hideo Akutsu, Izumi Yabuta, Masashi Hara, Hayuki Sugimoto, Takahisa Ikegami, Takeshi Watanabe,Toshimichi Fujiwara
FEBS letters, 2018, 592, 3173.

III
Achievements

O-33

Diverse Structural Conversion and Aggregation Pathways of
Alzheimer’s Amyloid-β (1-40)

Yuxi Lin, Bikash R Sahoo, Daisaku Ozawa, Misaki Kinoshita, Juhye Kang, Mi Hee Lim, Masaki Okumura,
Yang Hoon Huh, Eunyoung Moon, Jae Hyuck Jang, Hyun-Ju Lee, Ka-Young Ryu, Sihyun Ham,
Hyung-Sik Won, Kyoung-Seok Ryu, Toshihiko Sugiki, Jeong Kyu Bang, Hyang-Sook Hoe, Toshimichi Fujiwara,
Ayyalusamy Ramamoorthy, Young-Ho Lee
ACS nano, 2019, 13, 8766.
O-34

Structural characterization of the N-terminal kinase-interacting domainof an Hsp90-cochaperone Cdc37 by CD and solution NMR spectroscopy

Futoshi Ihama, Mami Yamamoto, Chojiro Kojima, Toshimichi Fujiwara, Katsumi Matsuzaki, Yoshihiko Miyata,
Masaru Hoshino
Biochimica et biophysica acta. Proteins and proteomics, 2019, 1867, 813.
O-35

A novel chitin-binding mode of the chitin-binding domain of chitinase A1
from Bacillus circulans WL-12 revealed by solid-state NMR

Hiroki Tanaka, Hideo Akutsu, Izumi Yabuta, Masashi Hara, Hayuki Sugimoto, Takahisa Ikegami, Takeshi Watanabe,Toshimichi Fujiwara
FEBS Letters, 2018, 592, 3173.

45

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O-36

Veratridine binding to a transmembrane helix of sodium channel Nav1.4 determinedby solid-state NMR
Ai Niitsu, Ayako Egawa, Keisuke Ikeda, Kazuo Tachibana, Toshimichi Fujiwara
Bioorganic & Medicinal Chemistry, 2018, 26, 5644.

O-37

Activities of the Consortium for Medicine, Chemistry, and Physics at Osaka University
Kazuya Kabayama, Kazuko Kaneda, Atsushi Shinohara, Yoshifumi Shirakami, Tadashi Watabe, Zijian Zhang,Atsushi Toyoshima, Takashi Yoshimura, Yoshiyuki Manabe, Atsushi Shimoyama, Koichi Fukase
J. Med. Imaging. Rad. Sci., 2019, 50, S40.

O-38

Observation of internal-conversion electrons emitted from 229mTh produced
by beta decay of 229Ac

Yudai. Shigekawa, Yoshitaka. Kasamatsu, Eisuke. Watanabe, Hidemi. Ninomiya, Sho. Hayami, Narumi. Kondo,
Yuki. Yasuda, Hiromitsu. Haba, Atsushi. Shinohara
Phys. Rev. C, 2019, 100, 44304.

O-39

X-ray pumping of the 229Th nuclear clock isomer

Takahiko Masuda, Akihiro Yoshimi, Akira Fujieda, Hiroyuki Fujimoto, Hiromitsu Haba, Hideaki Hara,
Takahiro Hiraki, Hiroyuki Kaino, Yoshitaka Kasamatsu, Shinji Kitao, Kenji Konashi, Yuki Miyamoto, Koichi Okai,
Sho Okubo, Noboru Sasao, Makoto Seto, Thorsten Schumm, Yudai Shigekawa, Kenta Suzuki, Simon Stellmer,
Kenji Tamasaku, Satoshi Uetake, Makoto Watanabe, Tsukasa Watanabe, Yuki Yasuda, Atsushi Yamaguchi,
Yoshitaka Yoda, Takuya Yokokita, Motohiko Yoshimura, Kojiro Yoshimura
Nature, 2019, 573, 238.
O-40

Transcriptional silencing of centromere repeatsby heterochromatin safeguards chromosome integrity.
Takuro Nakagawa, Akiko K Okita
Current Genetics, 2019, 65, 1089.

O-41

Heterochromatin suppresses gross chromosomal rearrangements at centromeresby repressing Tfs1/TFIIS-dependent transcription

Akiko K. Okita, Faria Zafar, Jie Su, Dayalini Weerasekara, Takuya Kajitani, Tatsuro S. Takahashi, Hiroshi Kimura,
Yota Murakami, Hisao Masukata, Takuro Nakagawa
Communications Biology, 2019, 2, 17.
O-42

Nucleosomes around a mismatched base pair are excluded via an Msh2-dependent
reaction with the aid of SNF2 family ATPase Smarcad1
Riki Terui, Koji Nagao, Yoshitaka Kawasoe, Kanae Taki, Torahiko L. Higashi, Seiji Tanaka, Takuro Nakagawa,
Chikashi Obuse, Hisao Masukata Tatsuro S. Takahashi
Genes & development, 2018, 32, 806.

O-43

Shelterin promotes tethering of late replication origins to telomeresfor replication-timing control

III

O-44

Achievements

Shiho Ogawa, Sayuri Kido, Tetsuya Handa, Hidesato Ogawa, Haruhiko Asakawa, Tatsuro S Takahashi,
Takuro Nakagawa, Yasushi Hiraoka, Hisao Masukata
The EMBO journal, 2018, 37, e98997.

First determination of Pu isotopes (239Pu, 240Pu and 241Pu) in radioactive particles
derived from Fukushima Daiichi Nuclear Power Plant accident

Junya Igarashi, Jian Zheng, Zijian Zhang, Kazuhiko Ninomiya, Yukihiko Satou, Miho Fukuda, Youyi Ni, Tatsuo Aono,
Atsushi Shinohara
Scientific Reports, 2019, 9, 11807.

O-45

福島原発周辺における土壌中放射性ストロンチウム濃度の分布測定
梶原知啓 , 二宮和彦 , 篠原厚 , 山口喜朗

Proceedings of the 20th Workshop on Environmental Radioactivity, 2019, 44.
O-46

福島県大熊町及び双葉町にて採取した放射性セシウムを含む不溶性粒子の分類
五十嵐淳哉 , 張子見 , 二宮和彦 , 篠原厚 , 佐藤志彦 , 箕輪はるか , 吉川英樹

Proceedings of the 20th Workshop on Environmental Radioactivity, 2019, 54
O-47

Atmospheric Activity Concentration of 90Sr and 137Cs
after the Fukushima Daiichi Nuclear Accident

Zijian Zhang, Kazuhiko Ninomiya, Yoshiaki Yamaguchi, Kazuyuki Kita, Haruo Tsuruta, Yasuhito Igarashi,
Atsushi Shinohara
Environ. Sci. Technol., 2019, 52, 9917.

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O-48

Fungal spore involvement in the resuspension of radiocaesium in summer

Yasuhito Igarashi, Kazuyuki Kita, Teruya Maki, Takeshi Kinase, Naho Hayashi,Kentaro Hosaka, Kouji Adachi,
Mizuo Kajino, Masahide Ishizuka, Tsuyoshi Thomas Sekiyama, Yuji Zaizen, Chisato Takenaka, Kazuhiko Ninomiya,
Hiroshi Okochi & Atsuyuki Sorimachi
Scientific Reports, 2019, 9, 1954.
O-49

Search for KL → π0ννand KL → π0X0 Decays at the J-PARC KOTO ExperimentJ. K. Ahn, B. Beckford, J. Beechert, K. Bryant, M. Campbell, S. H. Chen, J. Comfort, K. Dona, N. Hara, H. Haraguchi,
Y. B. Hsiung, M. Hutcheson, T. Inagaki, I. Kamiji, N. Kawasaki, E. J. Kim, J. L. Kim, Y. J. Kim, J. W. Ko,
T. K. Komatsubara, K. Kotera, A. S. Kurilin, J. W. Lee, G. Y. Lim, C. Lin, Q. Lin, Y. Luo, J. Ma, Y. Maeda, T. Mari,
T. Masuda, T. Matsumura, D. Mcfarland, N. McNeal, J. Micallef, K. Miyazaki, R. Murayama, D. Naito, K. Nakagiri,
H. Nanjo, H. Nishimiya, T. Nomura, M. Ohsugi, H. Okuno, M. Sasaki, N. Sasao, K. Sato, T. Sato, Y. Sato, H. Schamis,
S. Seki, N. Shimizu, T. Shimogawa, T. Shinkawa, S. Shinohara, K. Shiomi, S. Su, Y. Sugiyama, S. Suzuki, Y. Tajima,
M. Taylor, M. Tecchio, M. Togawa, Y. C. Tung, Y. W. Wah, H. Watanabe, J. K. Woo, T. Yamanaka, H. Y. Yoshida
Physical Review Letters, 2019, 021802.
O-50

Quantitative measurement of 219Rn radioactivity in exhaled breath from patients withbone metastasis of castration-resistant prostate cancer treated with 223RaCl2
Kazuhiro Ooe, Tadashi Watabe, Takashi Kamiya, Takashi Yoshimura, Makoto Hosono, Atsushi Shinohara,
Jun Hatazawa
EJNMMI Physics, 2019, 6, 13.

O-51

Volumetric and texture analysis on FDG PET in evaluating and predicting treatment
response and recurrence after chemotherapy in follicular lymphoma.

Mitsuaki Tatsumi, Kayako Isohashi, Keiko Matsunaga, Tadashi Watabe, Hiroki Kato, Yuzuru Kanakura, Jun Hatazawa
International journal of clinical oncology, 2019, 24, 1292.
O-52

Quantitative measurement of regional cerebral blood flow and oxygen metabolism in a
rat model of cerebral hypoperfusion
Hiroki Kato, Yasukazu Kanai, Tadashi Watabe, Hayato Ikeda, Genki Horitsugi, Jun Hatazawa
Brain research, 2019, 1719, 208.

O-53

MHC-mismatched Allotransplantation of Induced Pluripotent Stem Cell-Derived
Cardiomyocyte Sheets to Improve Cardiac Function
in A Primate Ischemic Cardiomyopathy Model

Noriyuki Kashiyama, Shigeru Miyagawa, Satsuki Fukushima, Takuji Kawamura, Ai Kawamura, Shohei Yoshida,
Seiko Eiraku, Akima Harada, Keiko Matsunaga, Tadashi Watabe, Koichi Toda, Jun Hatazawa, Yoshiki Sawa
Transplantation, 2019, 103, 1582.
O-54

Microvascular Dysfunction Related to Progressive Left Ventricular Remodeling due toChronic Occlusion of the Left Anterior Descending Artery in an Adult Porcine Heart
Shin Yajima, Shigeru Miyagawa, Satsuki Fukushima, Kayako Isohashi, Tadashi Watabe, Hayato Ikeda,
Genki Horitsugi, Akima Harada, Ryoto Sakaniwa, Jun Hatazawa, Yoshiki Sawa
International heart journal, 2019, 60, 715.

III

O-55

Achievements

Impact of 18F-PSMA-1007 uptake in prostate cancer using different peptide
concentrations: preclinical PET/CT study in mice

Fumihiko Soeda, Tadashi Watabe, Sadahiro Naka, Yuwei Liu, Genki Horitsugi, Oliver C Neels, Klaus Kopka,
Mitsuaki Tatsumi, Eku Shimosegawa, Frederik L Giesel, Jun Hatazawa
Journal of nuclear medicine, 2019, 60, 1594.

O-56

Enhancement of astatine-211 uptake via the sodium iodide symporterby the addition of ascorbic acid in targeted alpha therapy of thyroid cancer

Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuwei Liu, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima,
Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa
Journal of nuclear medicine, 2019, 60, 1301.
O-57

Preserved Cerebral Oxygen Metabolism in Astrocytic Dysfunction:
A Combination Study of 15O-Gas PET with 14C-Acetate Autoradiography

Carla Mari Macaisa, Tadashi Watabe, Yuwei Liu, Victor Romanov, Yasukazu Kanai, Genki Horitsugi, Hiroki Kato,
Eku Shimosegawa, Jun Hatazawa
Brain sciences, 2019, 9, 101.
O-58

Myeloid-Derived Suppressor Cells Infiltrate the Brain
and Suppress Neuroinflammation
in a Mouse Model of Focal Traumatic Brain Injury.

Sanae Hosomi, Yoshihisa Koyama, Tadashi Watabe, Mitsuo Ohnishi, Hiroshi Ogura, Toshihide Yamashita,
Takeshi Shimazu
Neuroscience, 2019, 406, 457.
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O-59

Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow
in rat xenograft models of C6 glioma and MIA PaCa-2
Masanao Aoki, Tadashi Watabe, Shushi Nagamori, Sadahiro Naka, Hayato Ikeda, Pornparn Kongpracha,
Genki Horitsugi, Yasukazu Kanai, Eku Shimosegawa, Yoshikatsu Kanai, Jun Hatazawa
Annals of nuclear medicine, 2019, 33, 394.

O-60

Simplified Dynamic Phantom for Pediatric Renography:
A Description of Instrument and its Performance

Takashi Kamiya, Tadashi Watabe, Koichi Fujino, Romanov Victor, Yoshiki Kawamura, Kayako Isohashi,
Keiko Matsunaga, Mitsuaki Tatsumi, Hiroki Kato, Eku Shimosegawa, Jun Hatazawa
Asia Oceania journal of nuclear medicine & biology, 2019, 7, 38
O-61

Inflammatory projections after focal brain injury trigger neuronal network disruption:
An 18F-DPA714 PET study in mice
Sanae Hosomi, Tadashi Watabe, Yuki Mori, Yoshihisa Koyama, Soichiro Adachi, Namiko Hoshi, Mitsuo Ohnishi,
Hiroshi Ogura, Yoshichika Yoshioka, Jun Hatazawa, Toshihide Yamashita, Takeshi Shimazu
NeuroImage. Clinical, 2018, 20, 946.

O-62

Preliminary feasibility study on differential diagnosis
between radiation-induced cerebral necrosis and recurrent brain tumor
by means of [18F]fluoro-borono-phenylalanine PET/CT

Rouaa Beshr, Kayako Isohashi, Tadashi Watabe, Sadahiro Naka, Genki Horitsugi, Victor Romanov, Hiroki Kato,
Shin-Ichi Miyatake, Eku Shimosegawa, Jun Hatazawa
Annals of nuclear medicine, 2018, 32, 702.
O-63

Transplantation of Human-induced Pluripotent Stem Cell-derived Cardiomyocytes Is
Superior to Somatic Stem Cell Therapy for Restoring Cardiac Function and Oxygen
Consumption in a Porcine Model of Myocardial Infarction
Masaru Ishida, Shigeru Miyagawa, Atsuhiro Saito, Satsuki Fukushima, Akima Harada, Emiko Ito, Fumiya Ohashi,
Tadashi Watabe, Jun Hatazawa, Katsuhisa Matsuura, Yoshiki Sawa
Transplantation, 2019, 103, 291.

O-64

Evaluation of the default-mode network by quantitative 15O-PET:
comparative study between cerebral blood flow and oxygen consumption

Jo Aoe, Tadashi Watabe, Eku Shimosegawa, Hiroki Kato, Yasukazu Kanai, Sadahiro Naka, Keiko Matsunaga,
Kayako Isohashi, Mitsuaki Tatsumi, Jun Hatazawa
Annals of nuclear medicine, 2018, 32, 485.

O-65

Application of astatine-210: Evaluation of astatine distribution and effectof pre-injected iodide in whole body of normal rats

Hayato Ikeda, Yoshihiko Hayashi, Naruto Takahashi, Tadashi Watabe, Yasukazu Kanai, Atsushi Shinohara,
Hiroki Kato, Hiroshi Watabe, Eku Shimosegawa, Jun Hatazawa
Applied radiation and isotopes: including data, 2018, 139, 251.
O-66

III
Achievements

A prostacyclin agonist and an omental flap increased myocardial blood flow
in a porcine chronic ischemia model

Shin Yajima, Shigeru Miyagawa, Satsuki Fukushima, Yoshiki Sakai, Kayako Isohashi, Tadashi Watabe, Hayato Ikeda,
Genki Horitsugi, Akima Harada, Ryoto Sakaniwa, Jun Hatazawa, Yoshiki Sawa
The Journal of thoracic and cardiovascular surgery, 2018, 156, 229.
O-67

Novel regenerative therapy combined with transphrenic peritoneoscopy-assisted
omentopexy

Satoshi Kainuma, Kiyokazu Nakajima, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Akima Harada,
Masashi Hirota, Yasuhiro Miyazaki, Noriyoshi Sawabata, Tadashi Watabe, Hiroshi Watabe, Koichi Toda,
Jun Hatazawa, Meinoshin Okumura, Yoshiki Sawa
Interactive cardiovascular and thoracic surgery, 2018, 26, 993.
O-68

X-ray angiography perfusion imaging with an intra-arterial injection:comparative study with 15O-gas/water positron emission tomography

Katsunori Asai, Hajime Nakamura, Tadashi Watabe, Takeo Nishida, Manabu Sakaguchi, Jun Hatazawa,
Toshiki Yoshimine, Haruhiko Kishima
Journal of neurointerventional surgery, 2018, 10, 780
O-69

Accuracy and Precision of Manual Segmentation of the Maxillary Sinus
in MR Images - a Method Study
Tobias N Andersen, Tron A Darvann, Shumei Murakami, Per Larsen, Yurie Senda, Anders Bilde,
Christian V Buchwald, Sven Kreiborg
British journal of Radiology, 2018, 91, 20170663.

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48

O-70

Does CBCT alter the diagnostic thinking efficacy, management and prognosis ofpatients with suspected Stage 0 medicationrelated osteonecrosis of the jaws?

Hiroaki Shimamoto, Tristan R Grogan, Tomomi Tsujimoto, Naoya Kakimoto, Shumei Murakami, David Elashoff,
Tara L Aghaloo, Sotirios Tetradis
Dentomaxillofacial Radiology, 2018, 47, 20170290.
O-71

Clinical guidelines for dental cone-beam computed tomography

Takafumi Hayashi, Yoshinori Arai, Toru Chikui, Sachiko Hayashi-Sakai, Kazuya Honda, Hiroko Indo,
Taisuke Kawai, Kaoru Kobayashi, Shumei Murakami, Masako Nagasawa, Munetaka Naitoh, Eiji Nakayama,
Yutaka Nikkuni, Hideyoshi Nishiyama, Noriaki Shoji, Shigeaki Suenaga, Ray Tanaka
Oral Radiology, 2018, 34, 89.
O-72

Neurofibromatosis Type 1 in the Mandible

Yuka Uchiyama, Tetsuro Sumi, Keisuke Marutani, Hiroo Takaoka, Shumei Murakami, Hiroyasu Kameyama,
Yoshiaki Yura
Ann Maxillofac Surg, 2018, 8, 121.
O-73

Effectiveness of the periodically rotated overlapping parallel lines withenhanced reconstruction (PROPELLER) techniquefor reducing motion artifacts caused by mandibular movements
on fat-suppressed T2-weighted magnetic resonance (MR) images

Hiroaki Shimamoto, Tomomi Tsujimoto, Naoya Kakimoto, Minami Majima, Yuri Iwamoto, Yurie Senda,
Shumei Murakami
Magnetic Resonance Imaging, 2018, 54, 1.
O-74

Gonial Angle Measured by Orthopantomography as a Predictorof Maximum Occlusal Force

Shunta Miwa, Masahiro Wada, Shumei Murakami, Tohru Suganami, Kazunori Ikebe, Yoshinobu Maeda
Journal of Prosthodontics, 2019, 28, e426.
O-75

T2 relaxation times of the retrodiscal tissue in patients with temporomandibular joint
disorders and in healthy volunteers: a comparative study
Naoya Kakimoto, Hiroaki Shimamoto, Jira Kitisubkanchana, Tomomi Tsujimoto, Yurie Senda, Yuri Iwamoto,
Rinus G Verdonschot, Yoko Hasegawa, Shumei Murakami
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2019, 128, 311.

O-76

Evaluation of mouthpiece fixation devices for head and neck radiotherapy patientsfabricated in PolyJet photopolymer by a 3D printer
Hideki Kitamori, Iori Sumida, Tomomi Tsujimoto, Hiroaki Shimamoto, Shumei Murakami, Masafumi Ohki
Physica Medica, 2019, 58, 90.

O-77

III

Comparative evaluation of bone microstructure in alveolar cleft repair by cone
beam CT: influence of different autologous donor sites and additional application of
β-tricalcium phosphate

Achievements

Kazuaki Miyagawa, Susumu Tanaka, Sachie Hiroishi, Yutaka Matsushita, Shumei Murakami, Mikihiko Kogo
Clinical Oral Investigations, 2019, 24, 2789.
O-78

小線源治療「舌がん・口腔がん治療の最前線」

村上秀明
耳鼻咽喉科・頭頸部外科 , 2019, 91, 1139.

O-79

口腔癌の高線量率小線源治療

柿本直也 , 村上秀明 , 清水谷公成
日本口腔腫瘍学会雑誌 , 2018, 30, 116.

O-80

Remediation of Groundwater Contaminatedby Heavy Metals Using Magnetic Separation TechniqueAlbino Jose Amosse, Yoko Akiyama
Journal of Physics: Conference Series, 2019, 1293, 12080.

O-81

Fundamental study on sustainable treatment system of mine waterusing magnetized solid catalyst
Chisato Mukuta, Yoko Akiyama
Progress in Superconductivity and Cryogenics (PSAC), 2019, 21, 15.

49

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O-82

Study on irradiation effect of insulating materials for fusion superconducting magnet:
Change in electric insulation performance by irradiation
Shunsuke Kito,Yoko Akiyama, Shigehiro. Nishijima
IOP Conference Series: Materials Science and Engineering, 2019, 502, 12195.

O-83

Design and fabrication of Ti-Zr-Hf-Cr-Mo and Ti-Zr-Hf-Co-Cr-Mo high-entropy alloys
as metallic biomaterials
Takeshi Nagase, Yuuka Iijima, Aira Matsugaki, Kei Ameyama, Takayoshi Nakano
Materials Science and Engineering: C, 2019, 107, 110322.

O-84

Development of Fe-Co-Cr-Mn-Ni-C high entropy cast iron (HE cast iron) available
for casting in air atmosphere
Takeshi Nagase, Tomoyuki Kakeshita, Kotaro Matsumura, Koichiro Nakazawa, Satoshi Furuya, Nobuaki Ozoe,
Katsumi Yoshino
Materials & Design, 2019, 184, 108172.

O-85

Development of Non-equiatomic Ti-Nb-Ta-Zr-Mo High-Entropy Alloys
for Metallic Biomaterials
TakaoHoria, Takeshi Nagasea, Mitsuharu Todai, Aira Matsugaki, Takayoshi Nakano
Scripta Materialia, 2019, 172, 83.

O-86

Alloy design and fabrication of ingots in Cu-Zn-Mn-Ni-Sn high-entropy
and Cu-Zn-Mn-Ni medium-entropy brasses
Takeshi Nagase, Akihiro Shibata, Mitsuaki Matsumuro, Mamoru Takemura, Satoshi Semboshi
Materials & Design, 2019, 181, 107900.

O-87

Investigation of ordered structure formation in Pt-Cu alloys using Materials Project,
ab initio calculation and high voltage electron microscopy
Takeshi Nagase, Takashi Nagase, Hiroyuki Motoki, K. Hagihara
AMTC Letters, 2019, 6, 78.

O-88

Solidification microstructures of the ingots obtainedby arc melting and cold crucible levitation melting in TiNbTaZr medium-entropy alloy
and TiNbTaZrX (X = V, Mo, W) high-entropy alloys
Takeshi Nagase, Kiyoshi Mizuuchi, Takayoshi Nakano
Entropy, 2019, 21, 483.

O-89

Additive manufacturing of dense components in beta-titanium alloys
with crystallographic texture from a mixture of pure metallic element powders
Takeshi Nagase, Takao Hori, Mitsuharu Todai, Shi-Hai Sun, Takayoshi Nakano
Materials & Design, Materials & Design, 2019, 173, 10771.

O-90

III
Achievements

Microstructure and Magnetic Properties of Cu-Ag-La-Fe Immiscible Alloys
with an Amorphous Phase
Takeshi Nagase, Tomoyuki Terai, Tomoyuki Kakeshita, Megumi Matsumoto, Yoshikazu Fujii
Materials Transactions, 2019, 60, 554.

O-91

Fabrication of the Beta-Titanium Alloy Rods from a Mixture ofPure Metallic Element Powders via Selected Laser Melting

Mitsuharu Todai, Takeshi, Nagase, Takao. Hori, Hiroyuki. Motoki, Shi-Hai Sun, Koji Hagihara, Takayoshi. Nakano
Materials Science Forum, 2018, 941, 1366.
O-92

Microstructure of Co-Cr-Fe-Mn-Ni-Ag and Co-Cr-Fe-Mn-Ni-Cu High Entropy Alloys
with Liquid Phase Separation
Takeshi Nagase
Materials Science Forum, 2018, 941, 1260.

O-93

Nuclei of BCC Phase in AlTi0.5ZrCuNiPd High Entropy Alloy
Takeshi Nagase, Akira Takeuchi, Kenji. Amiya
Microscopy, 2018, 67, i35.

O-94

Solidification Microstructure of Melt-Spun Ribbons
in Al-Mg-Li-Ca Medium Entropy Alloys

Takeshi Nagase, Akira Terayama, Takashi Nagaoka, Nobuyuki Fuyama, Kenji Amiya
Microscopy, 2018, 67, i25.

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50

O-95

Grain refinement of non-equiatomic Cr-rich CoCrFeMnNi high-entropy alloys throughcombination of cold rolling and precipitation of sigma phaseKen. Cho, Yumi. Fujioka, Takeshi Nagase, Hiroyuki Y. Yasuda
Materials Science and Engineering A, 2018, 735, 191.

O-96

Microstructure of equiatomic and non-equiatomic Ti-Nb-Ta-Zr-Mo high-entropy alloys
for metallic biomaterials
Takashi Nagase, Mitsuharu. Todai, Takao Hori, Takayoshi. Nakano
Journal of Alloys and Compounds, 2018, 753, 412.

O-97

Oxidation of Benzyl Alcohol over Nanoporous Au-CeO2 Catalysts Preparedfrom Amorphous Alloys and Effect of Alloying Au with Amorphous Alloys

Ai Nozaki, Tasuku Yasuoka, Yasutaka Kuwahara, Tetsutaro Ohmichi, Kohsuke Mori, Takeshi Nagase, Hiroyuki Y.
Yasuda, Hiromi Yamashita
Industrial & Engineering Chemistry Research, 2018, 57, 5599.
O-98

In situ atomic-level observation of the formation of platinum silicide
at platinum-silicon oxide interfaces under electron irradiation
Takeshi Nagase, Ryo Yamashita, Jung-Goo Lee
AIP Advances, 2018, 8, 55110.

O-99

Cu の分布に注目した球状黒鉛鋳鉄の電子顕微鏡観察

永瀬丈嗣 , 丸山徹 , 淺野和典 , 五十嵐芳夫
鋳造工学 , 2019, 91, 512.

O-100

球状黒鉛鋳鉄と球状黒鉛ハイエントロピー合金

永瀬丈嗣
金属 , 2019, 89, 899.

O-101

Al-Mg-Li-Ca 系軽量ミディアムエントロピー合金の合金設計と鋳造材の作製

永瀬丈嗣 , 寺山朗 , 長岡孝 , 府山伸行 , 阪本辰顕
鋳造工学 , 2019, 91, 717.

O-102

純元素粉末を用いたチタン合金の金属積層造形

永瀬丈嗣 , 當代光陽 , 中野貴由
鋳造工学 , 2019, 91, 627.

O-103

Ag-rich Ag-Cu-La-Fe 液体分離合金の組織と磁気的性質

永瀬丈嗣 , 寺井智之 , 掛下知行 , 森田健太
材料 , 2019, 68, 205.

O-104

走査透過電子顕微鏡を用いた球状黒鉛鋳鉄核物質の微量元素分布解明

永瀬丈嗣 , 丸山徹 , 五十嵐芳夫
日本金属学会会報・まてりあ , 2019, 58, 86.

III
Achievements

O-105

耐熱合金・生体合金として開発がすすむ 4 族・5 族・6 族元素からなる
ハイエントロピー合金の凝固組織

永瀬丈嗣 , 水内潔 , 當代光陽 , 中野貴由
日本金属学会会報・まてりあ , 2019, 58, 78.

51

IRS ANNUAL REPORT

2018-2019Biblio
B-1

Low-Dose-Rate Radiation Effects on Animals and Ecosystem -Long-Term Studyon the Fukushima Daiichi Nuclear Power Plant Accident?
Manabu Fukumoto, Hiroo Nakajima et al.
Springer, 2019, p.264 (221-235).

B-2

六極電場による配向制御分子ビーム生成とその表面反応への応用

岡田美智雄「最新 実用真空技術総覧」, エヌ・ティー・エス出版 , 2019, 第 3 章 第 1 節 , p734 (6 pages)

B-3

超重元素化学の最前線

豊嶋厚史 ( 分担執筆 )日本放射化学会 , 2019

B-4

錯体化合物辞典

吉村崇 ( 分担執筆 )朝倉書店 , 2019

B-5

PET/CT for Inflammatory Diseases Basic Sciences, Typical Cases, and Review, joint work
Tadashi Watabe et al.
Springer, 2019, p228.

B-6

歯科放射線学 第 6 版

村上秀明ほか共著
医歯薬出版株式会 , 2019, p503(6 pages)

B-7

口腔外科学 第 4 版

村上秀明ほか共著
医歯薬出版株式会 , 2019, p862(16 pages)

III
Achievements

IRS ANNUAL REPORT

2018-201952

PresentationP-1

アスタチン -211 標識金ナノ粒子の安定性評価

角永悠一郎 , 黄栩昊 , 張子見 , 兼田加珠子 , 大江一弘 , 寺本高啓 , 下山敦史 , 樺山一哉 , 豊嶋厚史 , 篠原厚 , 深瀬浩一
日本放射化学会第 63 回討論会（2019）P-2

アルファ線核医学治療に向けた At-211 標識アミノ酸誘導体の検討
張子見 , 兼田加珠子 , 豊嶋厚史 , 深瀬浩一 , 篠原厚
第 62 回放射化学討論会（日本放射化学会年会）

P-3

アミノ酸トランスポーター LAT1 を標的とするα線がんミサイル療法の開発

兼田加珠子 , 張子見 , 真鍋良幸 , 下山敦史 , 樺山一哉 , 白神宜史 , 金井好克 , 畑澤順 , 深瀬浩一 , 篠原厚
第 91 回日本生化学会大会

P-4

がん細胞型アミノ酸トランスポーターを標的とした新規核医学治療薬の開発

兼田加珠子 , 張子見 , 真鍋良幸 , 下山敦史 , 樺山一哉 , 金井好克 , 深瀬浩一 , 篠原厚
第 77 回日本癌学会学術総会

P-5

動物実験における短寿命アルファ線核種の体内外の分布

兼田加珠子 , 篠原厚 , 吉村崇 , 豊嶋厚史 , 張子見 , 永田光知郎 , 渡部直史 , 大江一弘 , 山村朝雄 , 白崎謙次 , 菊永英寿 , 羽場宏光 ,鷲山幸信
日本放射線安全管理学会 第 17 回 学術大会

P-6

がん細胞型アミノ酸トランスポーターを標的とした短寿命アルファ線核医学治療薬の開発

兼田加珠子 , 真鍋良幸 , 下山敦史 , 樺山一哉 , 金井好克 , 豊嶋厚史 , 深瀬浩一 , 篠原厚
第 78 回日本癌学会学術総会

P-7

短寿命α線核種を利用した癌治療プローブの開発

兼田加珠子 , 張子見 , 白神宜史 , 渡部直史 , 下山敦史 , 真鍋良幸 , 樺山一哉 , 豊嶋厚史 , 吉村崇 , 福田光宏 , 金井好克 , 畑澤順 ,
中野貴志 , 深瀬浩一 , 篠原厚
第 92 回 日本薬理学会年会

P-8

EVI1 によって制御される CGRP-CRLR/RAMP1 シグナルは白血病化を促進する

末金彰 , 齋藤 祐介 , 中畑新吾 , 小河穂波 , 市川朝永 , ナーウィンマナチャイ , マーチンジュリアナ , 兼田加珠子 , 大里元美 ,森下和広
第 77 回日本癌学会学術総会

P-9

SNX13 のハプロ不全は EVI1 高発現 AML の monosomy7 における原因遺伝子として白血病化に寄与している

小河穂波 , 末金彰 , 齋藤祐介 , 兼田加珠子 , ナーウィンマナチャイ , 森下和広
第 77 回日本癌学会学術総会

P-10

Carcinogenicity and genome variation in descendant mice
after the every generational low dose-rate internal 137Cs radiation exposure.
Hiroo Nakajima
The 9th Annual Meeting of the International Society of Radiation Neurobiology

IIIAchievements

P-11

Carcinogenicity and genome variation in descendant mice
after the every generational low dose-rate internal Cesium-137 radiation exposure.
Hiroo Nakajima, Uno Kazuko, Yoshisaki Yamaguchi, Tsuyoshi Todo.
16th International Congress of Radiation Research (ICRR2019)

P-12

低線量率のセシウム -137 放射線内部被曝は発がんや継世代影響にほとんど寄与しない可能性がある
中島裕夫 , 宇野賀津子 , 山口喜朗 , 藤堂剛 , 米倉義晴 , 篠原厚

The 6th Asian Congress on Environmental Mutagens (ACEK) and the 48th Annual Meeting of the JapaneseEnvironmental Mutagen Society (JEMS)
P-13

多世代にわたり低線量 137Cs 内部被曝した A / J および B6 マウスにおける全ゲノム解析

中島裕夫 , 大野みずき , 石原弘 , 鈴木正敏 , 遠藤曉 , 遠藤大二 , 續輝久 , 藤堂剛
日本放射線影響学会第 61 回大会

P-14

多世代にわたり低線量 137Cs 内部被曝した A / J および B6 マウスにおける全ゲノム解析
中島裕夫 , 藤堂剛 , 鈴木正敏 , 遠藤曉 , 遠藤大二
日本環境変異原学会 , 第 47 回大会

P-15

短寿命アルファ線放出核種 At-211 の合理的規制に向けた飛散率測定

豊嶋厚史 , 篠原厚 , 吉村崇 , 兼田加珠子 , 張子見 , 永田光知郎 , 渡部直史 , 大江一弘 , 山村朝雄 , 白崎謙次 , 菊永英寿 , 羽場宏光 ,鷲山幸信
日本放射線安全管理学会 第 17 回 学術大会

53

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P-16

寿命アルファ線核種の合理的規制のためのラジウム -223 およびその子孫核種の飛散率等の測定

永田光知郎 , 吉村崇 , 豊嶋厚史 , 篠原厚 , 兼田加珠子 , 張子見 , 渡部直史 , 大江一弘 , 山村朝雄 , 白崎謙次 , 菊永英寿 , 羽場宏光 ,鷲山幸信
日本放射線安全管理学会 第 17 回 学術大会

P-17

Synthesis and Photophysical Properties of Tricyanidonitridorhenium(V) Complexes
with Bipyridine Derivatives
Kojiro Nagata, Naoko Otsuji, Soichiro Akagi, Sho Fujii, Noboru Kitamura, Takashi Yoshimura.
International Symposium on Technetium and Rhenium.

P-18

塩化ラジウム -223 水溶液から飛散する核種の同定及び定量

永田光知郎 , 白崎謙次 , 豊嶋厚史 , 大江一弘 , 山村朝雄 , 篠原厚 , 吉村崇
第 64 回放射化学討論会

P-19

ラリアート型クラウンキレーターによる放射性アルカリ土類金属錯体の合成
永田光知郎 , 矢島辰雄 , 吉村崇
錯体化学会第 69 回討論会

P-20

At-211 標識 RGD ペプチドの作製と基礎的検

小川数馬 , 武田拓也 , 三代憲司 , 越後拓亮 , 吉村崇 , 篠原厚 , 柴和弘 , 絹谷清剛 , 小谷

JSMI2018.
P-21

Chemical properties of 211At-NaAt and its biological behaviors in small animals.
Yoshifumi Shirakami, Victor Romanov, Tadashi Watabe, Kazuko Kaneda, Yuwai Liu, Atsushi Shinohara,
Eku Shimosegawa, Jun Hatazawa.
第 58 回 日本核医学会学術総会

P-22

がん間質を標的とするα線治療薬 255Ac-FAPI-04 の研究

白神宜史 , 渡部直史 , Yuwei Liu, 兼田加珠子 , 永田光知郎 , 豊嶋厚史 , 下瀬川恵久 , 篠原厚 , 畑澤順 , Frederik Giesel
第 3 回放射性薬品科学研究会／第 19 回放射性医薬品・画像診断薬研究会

P-23

Radiolabeling of small molecules with astatine (211At) for theranostics.,
Shirakami Yoshifumi
BER2018

P-24

A new method for the preparation of astatine-211(211At) andiodine-123(123I) labelled amino acid analogues of phenylalanine, 211At-Phe and 123I-Phe,for radionuclide therapy and SPECT imaging applications
Shirakami Yoshifumi
EANM2018

P-25

Preparation of aqueous solution of 211At-sodium astatide (Na211At)
in a high radiochemical purity and its biodistribution study in rats.

III

P-26

Achievements

Shirakami Yoshifumi
WFNMB2018

アスタチン (211At) の酸化還元反応とα線治療薬の創薬研究
白神宜史
第 2 回日本核医学会分科会放射薬品科学研究会

P-27

法令報告に至らなかった事故トラブル事例阪大 RCNP 2017 ‐ 2018鈴木智和 , 吉村崇 , 高橋賢臣 , 福田光宏 , 嶋達志 , 依田哲彦
日本放射線安全管理学会学術大会講演予稿集

P-28

阪大 RCNP の教育訓練ガイドライン

鈴木智和
第 16 回日本放射線安全管理学会 6 月シンポジウム

P-29

密封されてない放射性同位元素使用施設における半減期が非常に長い放射線を放出する同位元素の法解釈の検討
鈴木智和 , 髙橋賢臣 , 青井考
第２回日本放射線安全管理学会・日本保健物理学会合同大会

IRS ANNUAL REPORT

2018-2019

54

P-30

阪大 RCNP の放射線安全インターロックの概要と運用上の課題
鈴木智和
第 7 回加速器安全シンポジウム

P-31

長半減期同位体 144Nd が安定同位体として非密封 RI 施設に持ち込まれた事例の報告
鈴木智和 , 髙橋賢臣 , 青井考
令和元年度日本アイソトープ協会放射線安全取扱部会年次大会

P-32

Photoluminescence of Nitridorhenium(V) Complexes

Takashi YoshimuraInternational Symposium on Technetium and Rhenium 2018 年 10 月 招待有り
P-33

α線、β線治療 ; 基礎から臨床への創薬プロセス -from bench to bedside短寿命アルファ線放出核種の合理的な安全規制のための研究
吉村崇
第 59 回日本核医学会学術総会、第 39 回日本核医学技術学会総会学術大会

P-34

Ra-0223 及び Rn-219 の飛散率の測定と短寿命アルファ線放出核種等の安全規制に関するガイドライン等作成

吉村崇
東北大学金属材料研究所附属量子エネルギー材料科学国際研究センター 2019 年度大洗アルファ合同研究会

P-35

トリアミノシクロヘキサン骨格を有する三脚型キレートランタノイド錯体の合成
石田陽太 , 永田光知郎 , 吉村崇
錯体化学会第 69 回討論会

P-36

大学等放射線施設協議会による女性の放射線業務従事者の被ばく管理に関するアンケート
吉村崇2018 年度大学等放射線施設協議会

P-37

発光スイッチングするレニウム・テクネチウム錯体
吉村崇
長崎大学化学・物質工学セミナー

P-38

阪大における放射線安全管理と規制に関する研究
吉村崇2018 年度東北大学金属材料研究所放射線教育訓練

P-39

結合生成・解離を利用して発光スイッチングする金属錯体
吉村崇2018 年度平塚シンポジウム

P-40

III

大阪大学放射線科学基盤機構の紹介
吉村崇2018 年度北海道地区大学等放射線施設協議会

Achievements

P-41

非密封放射線施設の拠点化

吉村崇2018 年度日本アイソトープ協会安全取扱部会

P-42

Preparation of novel anticancer drugs using At-211
Kazuya Kabayama
Naposaka 2nd workshop

P-43

Preparation of novel anticancer drugs using At-211
Kazuya Kabayama
The Fifth Asian Chemical Biology Conference (ACBC-5)

P-44

難治性がん治療のための短寿命 RI 標識分子の合成と利用

樺山一哉 , 兼田加珠子 , 張子見 , 真鍋良幸 , 下山敦史 , 豊嶋厚史 , 篠原厚 , 深瀬浩一
第 12 回バイオ関連化学シンポジウム（第 33 回生体機能関連化学シンポジウム , 第 21 回バイオテクノロジー部会シンポジウム）

P-45

短寿命α線核種を利用した新規抗がん剤の創製

樺山一哉 , 兼田加珠子 , 張子見 , 真鍋良幸 , 下山敦史 , 豊嶋厚史 , 篠原厚 , 深瀬浩一
第 41 回日本分子生物学会年会

55

IRS ANNUAL REPORT

2018-2019P-46

水溶液中におけるボロノ基 - アスタチン交換反応の特異性の解明

尾幡穂乃香 , 白神宜史 , 兼田加珠子 , 大江一弘 , 永田光知郎 , 寺本高啓 , 市村聡一朗 , 中川創太 , 吉村崇 , 豊嶋厚史 , 篠原厚
日本放射化学会第 63 回討論会

P-47

短寿命アルファ線核種 Ac-225 の合理的規制に向けた飛散率測定

山村朝雄 , 白崎謙次 , 坂本清志 , 菊永英寿 , 鷲山幸信 , 篠原厚 , 吉村崇 , 豊嶋厚史 , 兼田加珠子 , 張子見 , 永田光知郎 , 渡部直史 ,大江一弘 , 羽場 宏光
日本放射線安全管理学会 第 17 回 学術大会

P-48

短寿命α線核種の合理的規制のためのデータ取得による安全性検証と安全管理・教育方法の開発

篠原厚 , 吉村崇 , 豊嶋厚史 , 兼田加珠子 , 張子見 , 永田光知郎 , 渡部直史 , 大江一弘 , 畑澤順 , 山村朝雄 , 白崎謙次 , 菊永英寿 ,羽場宏光 , 鷲山幸信
第 62 回放射化学討論会（日本放射化学会年会）

P-49

Ko Nishikawa and Kaon Experiments
Taku Yamanaka
Koichiro Nishikawa Memorial Symposium

P-50

J-PARC KOTO

Taku Yamanaka
NTU HEP April Flavor/Collider Workshop
P-51

Introduction to KAON2019 - Experiments -Taku Yamanaka
KAON2019, International Conference on Kaon Physics 2019
P-52

Enhancement of At-211 uptake in the thyroid gland: SPECT study in rats.

Yuwei Liu, Tadashi Watabe, Kazuko Kaneda-Nakashima, Yoshifumi Shirakami, Atsushi Toyoshima, Mitsuaki Tatsumi,
Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa.
日本分子イメージング学会第 13 回学会総会・学術集会 .
P-53

Enhancement of astatine-211 uptake via the sodium iodide symporterby the addition of ascorbic acid in targeted alpha therapy of thyroid cancer

Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuwei Liu, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima,
Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa
第 14 回日本分子イメージング学会総会・学術集会
P-54

Targeted Alpha Therapy using Astatine-211 for Thyroid Cancer.

Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuwei Liu, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima,
Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa.
The 6th Rising Nuclear Medicine Professional Challenge (AOCNMB 2019)
P-55

Targeted alpha therapy using astatine (211At) labelled phenylalanine:preclinical study in glioma xenograft mice

III

P-56

Achievements

Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuwei Liu, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima,
Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa.
European Assocciation Nuclear Medicine (EANM) congress 2019

Theranostics targeting fibroblast activation protein in the tumor stroma:[64Cu] and [225Ac] labelled FAPI-04 in pancreatic cancer xenograft mice

Tadashi Watabe, Yoshifumi Shirakami, Kazuko Kaneda-Nakashima, Yuwei Liu, Thomas Lindner, Kazuhiro Ooe,
Atsushi Toyoshima, Sadahiro Naka, Eku Shimosegawa, Uwe Haberkorn, Frederik Giesel, Jun Hatazawa.
European Assocciation Nuclear Medicine (EANM) congress 2019
P-57

Enhancement of astatine (211At) uptake via the sodium iodide symporterby the addition of ascorbic acid in targeted alpha therapy of thyroid cancer

Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuwei Liu, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima,
Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa.
Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2019 Annual Meeting
P-58

Targeted alpha therapy of thyroid cancer: evaluation of [At-211]NaAt treatmentin the xenograft model.

Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuwei Liu, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima,
Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa.
第 59 回日本核医学会学術総会

IRS ANNUAL REPORT

2018-2019

56

P-59

放射線の種類弁別可能なイメージング装置開発とα線分布計測への応用

山本誠一 , 渡部直史 , 兼田加珠子 , 白神宣史 , 大江一弘 , 篠原厚 , 豊嶋厚史 , 畑澤順
第 14 回日本分子イメージング学会総会・学術集会

P-60

Increased uptake of At-211 in thyroid gland by the preparation
with ascorbic acid for targeted alpha therapy of thyroid cancer

Kazuhiro Ooe, Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuwei Liu, Yoshifumi Shirakami, Atsushi Toyoshima,
Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa.
The 11th International Symposium on Targeted-Alpha-Therapy (TAT11)
P-61

Dissolution of dry distilled At-211 with non-toxic aqueous solutions

Kazuhiro Ooe, Tadashi Watabe, Yoshifumi Shirakami, Soichiro Ichimura, Honoka Obata, Takumi Ikeda, Zijian Zhang,
Kojiro Nagata, Atsushi Toyoshima, Takashi Yoshimura, Atsushi Shinohara, Jun Hatazawa.
Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2019 Annual Meeting
P-62

Ra-223 投与患者の呼気に排泄される Rn-219 放射能量の定量
大江一弘 , 渡部直史 , 神谷 貴史 , 吉村 崇 , 細野 眞 , 篠原厚 , 畑澤 順
第 59 回日本核医学会学術総会

P-63

治療用アルファ線核種 At-211 の乾式分離後の溶出条件の検討

大江一弘 , 渡部直史 , 白神宜史 , 市村聡一朗 , 池田卓海 , 張子見 , 永田光知郎 , 豊嶋厚史 , 吉村崇 , 篠原厚 , 畑澤順
第 58 回日本核医学会学術総会

P-64

Current interstitial brachytherapy for tongue cancer

Shumei Murakami.
CNUSD & CNUDH International Symposium: Dental Education & Science
P-65

A quantitative analysis of susceptibility artifact on MRI due to orthodontic materials
Yuri Iwamoto, Shumei Murakami, Hajime Fuchihata.
CNUSD & CNUDH International Symposium: Dental Education & Science

P-66

Diagnostic imaging in oral and maxillofacial region
Shumei Murakami,International forum between Chinese and Japanese Medicine

P-67

MRI in Oral region

Shumei Murakami.
Current and Future Challenges in DentistryP-68

Susceptibility artifact caused by orthodontic wires
Shumei Murakami, Yuri Iwamoto.
3D-Lab Seminar 2019

P-69

III

MRI application onto oral and maxillofacial region

Achievements

Shumei Murakami
Rigshospitalet 2019 Symposium
P-70

Radiation therapy; special thanks to Dr. Niels Bohr
Shumei Murakami
Niels Bohr Institute special seminar

P-71

CT in oral region

Shumei Murakami, Yuri Iwamoto.
2019 Danish Dental Association Special Seminar
P-72

Stereoscopy

Shumei Murakami, Yuri Iwamoto.
2019 Danish Dental Association Special Seminar
P-73

Current interstitial brachytherapy for tongue cancer
Shumei Murakami, Yuri Iwamoto.
2019 Danish Dental Association Special Seminar

P-74

Metallic artifact caused by orthodontic wire
Yuri Iwamoto, Shumei Murakami.,
2019 Danish Dental Association Special Seminar

57

IRS ANNUAL REPORT

2018-2019

P-75

Radiation exposure at NPP and dental practice
Shumei Murakami, Yuri Iwamoto2019 Danish Dental Association Special Seminar

P-76

唾液腺疾患、外傷、顎関節疾患

村上秀明
日本歯科放射線学会 , ステップアップ講習会

P-77

MRI の基礎村上秀明
日本歯科放射線学会 , MRI 研修会

P-78

舌癌の画像診断と放射線治療

村上秀明
大阪大学放射線医学教室同門会 , 特別講演

P-79

包括的口腔がん治療最前線 , 口腔がんの放射線治療
村上秀明
大阪大学歯学部同窓会第 96 回学術講演会

P-80

口腔領域の画像診断と放射線被曝
村上秀明
兵庫県同窓会講演会

P-81

歯科放射線治療医村上秀明
第 31 回日本放射線腫瘍学会

P-82

大学入試の放射線物理村上秀明
第 60 回日本歯科放射線学会学術大会

P-83

放射線の有効利用と被曝による影響
村上秀明
大阪府婦人歯科医師会

P-84

放射線治療におけるα線の利用
村上秀明
第 24 回臨床画像大会

P-85

放射線治療ー舌癌に対する小線源治療
村上秀明
中日医学交流フォーラム

P-86

III

歯科・口腔領域での放射線の利用

P-87

Achievements

村上秀明
大阪府保険医協会

歯周病と CKD

村上秀明 , 岩本悠里
大阪大学腎臓内科研修会

P-88

Biochemical analysis of DNA polymerase actions across the trinucleotide repeats
Asako Furukohri
第 92 回日本生化学会大会

P-89

DNA 二本鎖切断修復機構で働くヒト Mre11/Ra50/Nbs1 複合体の動的構造解析
古郡麻子
第 42 回日本分子生物学会大会

P-90

DNA 二本鎖切断修復機構で働くヒト MRN 複合体の動的構造解析
古郡麻子
第 25 回 DNA 複製・修復・組換えワークショップ

P-91

DNA 二本鎖切断修復機構で働く Mre11/Rad50/Nbs1 複合体の動的構造解析
古郡麻子
第 41 回日本分子生物学会年会

IRS ANNUAL REPORT

2018-2019

58

P-92

DNA 二本鎖切断修復機構で働く Mre11/Rad50/Nbs1 複合体の構造と機能
古郡麻子
第 91 回日本生化学会大会

P-93

DNA 二本鎖切断修復機構で働く Mre11/Rad50/Nbs1 複合体の構造と機能
古郡麻子
日本遺伝学会第 90 回大会

P-94

The development of novel Ti-Zr-Hf-Co-Cr-Mo bio-high entropy alloy
Yuuka Iijima, Takashi Nagase, Aira Matsugaki, Kei Ameyama, Takayoshi Nakano.
Harmonic 2019, 4th International Symposium on Hetero Structure and Advanced Materials

P-95

Development of biomedical be-ta Ti alloys by additive manufacturing from Mixture
powderMitsuharu Todai, Risa Kato, Takashi Nagase, Takayoshi Nakano.
The World Conference on Titanium 2019 (Ti-2019)

P-96

Solidification microstructure analysis in AlTi0.5ZrCuNiPd High Entropy Glasses
and High Entropy Alloys
Takashi Nagase, Akira Takeuchi, Kenji Amiya, Takeshi Egami
粉体粉末冶金協会 平成 31 年度春季大会

P-97

STEM Observation on Spheroidal Graphite Cast Iron Focusing on Inclusions
Takashi Nagase, Toru Maruyama, Yoshio Igarashi.
日本鋳造工学会第 173 回全国講演大会

P-98

STEM observation of Nuclei in High Entropy Alloys
Takashi Nagase, Akira Takeuchi, Kenji Amiya, Takeshi Egami.
日本鋳造工学会第 173 回全国講演大会

P-99

Development of equi-atomic TiNbTaZrMo high entropy alloys for metallic biomaterials
Takashi Nagase, Mitsuharu Todai, Takayoshi Nakano.
The Second International Conference on High-Entropy Materials (ICHEM 2018)

P-100

Solidification Microstructure of Ti-Ag and Ti-Ag-Nb Immiscible Alloys Focusing
on the Formation of Intermetallic Compounds
Takashi Nagase.
MRS 2018 Fall Meeting

P-101

STEM Observation of Spheroidal Graphite Cast Iron focusing on the elemental
distribution
Takashi Nagase, Toru Maruyama,Yoshio Igarashi.
The 7th Japan-Korea Conference for Young Foundry Engineers

III

P-102

Achievements

Development of FexCoCrMnNiCy high entropy alloys for casting under air atmosphereTakashi Nagase, Tomoyuki Kakeshita, Kotaro Matsumura, Koichiro Nakazawa, Satoshi Furuya, Nobuaki Ozoe,
Katsumi Yoshino.
日本鋳造工学会第 172 回全国講演大会

P-103

Fabrication of the beta-titanium alloy rods from a mixture of pure metallic element
powders via selected laser melting
Mitsuharu Todai, Takashi Nagase, Takao Hori, Hiroyuki Motoki, Shi-Hai Sun, K. Hagihara, Takayoshi Nakano.,International Conference on Processing & Manufacturing of Advanced Materials 2018 (Thermec 2018)

P-104

Microstructure of High Entropy Alloys with Liquid Phase Separation

Takashi Nagase.
International Conference on Processing & Manufacturing of Advanced Materials 2018 (Thermec 2018)
P-105

Application of Fe-based amorphous alloys for the in situ TEM observationof the nucleation and growth of bcc-Fe dendrite
Takashi Nagase.
The 12th international conference on bulk metallic glasses(BMG 12)

P-106

Influence of casting process on the solidification microstructure of
TiNbTaZrMo high-entropy alloys for metallic biomaterials
Takashi Nagase, Kiyoshi Mizuuchi, Takayoshi Nakano
The 171th meeting of Japan Foundary Society (JFS)59

IRS ANNUAL REPORT

2018-2019P-107

生体用ハイエントロピー合金の合金設計ならびに組織制御の指針
中野加菜 , 永瀬丈嗣 , 當代光陽 , 中野貴由
第 133 回金属物性研究会ならびに軽金属学会支部研究会

P-108

Pre-alloyed 粉末を使用しない金属積層造形とこれを利用した生体用チタン合金の開発
當代光陽 , 永瀬丈嗣 , 中野貴由
第 133 回金属物性研究会ならびに軽金属学会支部研究会

P-109

状態図を利用したチタン鋳造合金の開発
永瀬丈嗣
日本鋳造工学会関西支部 2019 年秋季講演大会

P-110

ハイエントロピー黄銅の材料設計とその特性
永瀬丈嗣 , 柴田顕弘 , 松室光昭 , 武村守 , 千星聡
日本銅学会第 59 回講演大会

P-111

Materials project を利用したアモルファス合金・ハイエントロピー合金の設計
永瀬丈嗣
日本材料学会・第 5 回材料 WEEK

P-112

球状黒鉛鋳鉄のラマン分光法

永瀬丈嗣 , 鴨井督 , 松村浩太郎 , 中澤耕一郎 , 古屋諭 , 尾添伸明 , 吉野勝美 , 丸山徹 , 五十嵐芳夫
日本鋳造工学会第 174 回全国講演大会

P-113

持ち運び可能な金属の凝固・鋳造の体験実習教材の開発
永瀬丈嗣
日本金属学会 2019 年秋期講演大会

P-114

Ti-Zr-Hf-Co-Cr-Mo 生体ハイエントロピー合金の組織と特性
飯島佑香 , 永瀬丈嗣 , 松垣あいら , 飴山惠 , 中野貴由
日本金属学会 2019 年秋期講演大会

P-115

生体用 bcc 型ハイエントロピー合金におけるヤング率
川堀龍 , 當代光陽 , 永瀬丈嗣 , 中野貴由
日本金属学会 2019 年秋期講演大会

P-116

BCC-Fe デンドライト核生成・成長の透過電子顕微鏡その場観察
永瀬丈嗣
日本鋳造工学会関西支部 第 25 回関西鋳造懇話会

P-117

BCC-Fe デンドライト成長初期過程の電顕その場観察
永瀬丈嗣
日本顕微鏡学会第 75 回学術講演会

P-118

III
Achievements

混合エンタルピーの観点からみた金属ガラス・ハイエントロピー合金（3d-HEA, RHEA, LW-HEA, HE Brass）の特徴
永瀬丈嗣 , 寺山朗 , 長岡孝 , 府山伸行 , 阪本辰顕 , 柴田顕弘 , 松室光昭 , 武村守 , 千星聡
粉体粉末冶金協会 , 平成 31 年度春季大会

P-119

新生体用ハイエントロピー合金の開発と細胞との相互作用
永瀬丈嗣
新学術領域研究・ハイエントロピー合金 2019 年度スタートアップ会議

P-120

Refractory High Entropy Alloy (RHEA) の合金状態図と凝固組織
永瀬丈嗣 , 水内潔 , 當代光陽 , 中野貴由
日本学術振興会 合金状態図 172 委員会 第 36 回研究会

P-121

Materials Project を利用した鋳造合金の合金設計
永瀬丈嗣
日本鋳造工学会関西支部 2018 年秋季講演大会

P-122

球状黒鉛鋳鉄の微細組織 : 走査透過電子顕微鏡 (STEM) と Materials Project
永瀬丈嗣
第 6 回関西鋳造技士会

IRS ANNUAL REPORT

2018-201960

P-123球状黒鉛鋳鉄と球状黒鉛ハイエントロピー合金に関する研究
永瀬丈嗣
日本金属学会 2019 年春期講演大会

P-124

Ti-Zr-Hf-Co-Cr-Mo 系生体ハイエントロピー合金の開発
飯島佑香 , 永瀬丈嗣 , 松垣あいら , 石本卓也 , 飴山惠 , 中野貴由
日本金属学会 2019 年春期講演大会

P-125

CoCuFeMnNi および CoCrCuFeMnNi ハイエントロピー合金の液体分離現象
永瀬丈嗣
第 23 回関西大学先端科学技術シンポジウム

P-126

Ti-Zr-Hf-Co-Cr-Mo 系生体ハイエントロピー合金の合金設計
飯島佑香 , 永瀬丈嗣 , 松垣あいら , 石本卓也 , 飴山惠 , 中野貴由
平成 30 年度第 2 回材料物性工学談話会講演会・ポスター発表会

P-127

等原子組成比・非等原子組成比 Mg-Al-Cu-Zn-Sn 軽量ハイエントロピー合金の合金設計と鋳造法による試作
永瀬丈嗣 , 柴田顕弘 , 松室光昭 , 武村守
軽金属学会第 135 回秋期大会

P-128

ハイエントロピー鋳造黄銅の開発
永瀬丈嗣
日本銅学会第 58 回講演大会

P-129

アモルファス合金を利用することで可能となるデンドライト核生成・成長のナノスケールその場観察
永瀬丈嗣
日本材料学会 第 4 回材料 WEEK

P-130

生体材料としてのハイエントロピー合金の可能性とその設計
當代光陽 , 永瀬丈嗣 , 川堀龍 , 松垣あいら , 中野貴由
日本金属学会 2018 年秋期講演大会

P-131

HfNbTaTiZr 合金の相変態挙動および力学特性に及ぼすβ安定化元素の影響
山田祐介 , 趙研 , 永瀬丈嗣 , 安田弘行
日本金属学会 2018 年秋期講演大会

P-132

軽量ハイエントロピー鋳造合金の検討
永瀬丈嗣 , 寺山朗 , 長岡孝 , 府山伸行 , 阪本辰顕
日本金属学会 2018 年秋期講演大会

P-133

III

走査透過電子顕微鏡（STEM）による球状黒鉛鋳鉄の微細組織観察
永瀬丈嗣 , 丸山徹 , 五十嵐芳夫
日本鋳造工学会関西支部 , 第 22 回鋳造懇話会

Achievements

P-134

ハイエントロピー合金の特徴と鋳造合金としての実用化に向けた研究
永瀬丈嗣
日本学術振興会鋳物 24 委員会・鋳造プロセス分科会 第 20 回会議

P-135

球状黒鉛ハイエントロピー合金の開発

永瀬丈嗣 , 掛下知行 , 松村浩太郎 , 中澤耕一郎 , 古屋諭 , 尾添伸明 , 吉野勝美
日本鋳造工学会第 171 回全国講演大会

P-136

凝固組織が冷却速度依存性を示す AlCoCu0.3FeNi ハイエントロピー合金
永瀬丈嗣 , 掛下知行 , 田村卓也
日本鋳造工学会第 171 回全国講演大会

61

IRS ANNUAL REPORT

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AwardA-1

17th Annual meeting best poster presentation

Japanese Society of Radiation Safety Management
Kazuko Kaneda-Nakashima, Atsushi Shinohara, Takashi Yoshimura, Atsushi Toyoshima, Zijian Zhang,
Kojiro Nagata, Tadashi Watabe, Kazuhiro Ooe, Tomoo Yamamura, Kenji Shirasaki, Hidetoshi Kikunaga,
Hiromitsu Haba, Koushin Washiyama
A-2

JSNM 6th returnee award
Japan Society of Nuclear Medicine
Tadashi Watabe

A-3

6th Rising Nuclear Medicine Professional Challenge Gold award (1st prize)
The 13th Asia Oceania Congress of Nuclear Medicine and Biology, AOCNMB2019
Tadashi Watabe

A-4

大阪大学医学部放射線医学教室同門会優秀論文賞（銀賞）
大阪大学医学部
渡部直史

A-5

優秀論文賞

日本歯科放射線学会
島本博彰 , 辻本友美 , 柿本直也 , 眞嶋みなみ , 岩本悠里 , 千田百合絵 , 村上秀明

A-6

第１回学術賞

環境放射能除染学会
秋山庸子 , 西嶋茂宏

A-7

日本金属学会功績賞（工業材料部門）
日本金属学会永瀬丈嗣

Social Contribution
S-1

教育訓練検討委員会委員（公財）日本アイソトープ協会
鈴木智和

S-2

III

放射線取扱主任者の資質の向上を図るための講習講師

S-3

Achievements

日本放射線安全管理学会
鈴木智和

放射線業務従事者の教育訓練（公財）日本アイソトープ協会放射線安全取扱部会中部支部
鈴木智和

IRS ANNUAL REPORT

2018-201962

Fund for Preparation of New Education and Research Projects
新規教育研究プロジェクト準備経費について
現在、放射線科学基盤機構では、放射線の生物学的影響、福島関連研究、大規模 RI 製造法など、アルファ線

核医学治療に続く新たな教育研究プロジェクトの立ち上げに取り組んでいる。これらを遂行するためには、理学研究科や医学系研究科などの部局内や学内に留まらない学際的な意見の交流が重要である。プロジェクトの計画段階で各分野の多様な意見を集約、精査することでプロジェクトを取り巻く環境を把握し、それに基づいた計画を立案することが必要だからである。そのため、本機構では、専任教員ならびに兼任教員が新たな教育
研究プロジェクトの立上げを行うための準備活動を積極的に支援している。2019 年度から計画立案者に対する支援を行うために「教育研究プロジェクト準備経費」を策定し、公募を行っている。2019 年度は以下の 4 件の課題を採択し、支援を行なった。

• 特殊抗体を用いたアルファ線核医学治療薬の検討• BNCT のための小型の中性子発生装置の開発• 加速器 RI 応用研究を推進する大規模製造の分野横断的連携体制の構築• 核医学治療の最適化をめざす分野横断的研究体制の構築
これらの採択課題では、大阪大学だけではなく、東北大学、理化学研究所、量子科学技術研究開発機構、関西大学、大阪国際がんセンターなど多くの機関の研究者が参画し、有意義な意見交換が交わされ、プロジェク
トを計画立案するための課題の抽出が行われた。一部の採択課題では、COVID-19 の影響により、当初予定していた意見交換の場であるワークショップやシンポジウムの開催を計画通りに遂行することは叶わなかった。
そのため、来年度には、その課題を継続させて Web を活用しての交流会の開催を予定している。
本取り組みは、放射線科学基盤機構の発展に留まらず、放射線科学関連分野の活性化に資する重要な活動の一つとして位置付け、今後も継続的な支援を行う予定である。

III
Achievements
63

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特殊抗体を用いたアルファ線核医学治療薬の検討
代表者
参画研究者

兼田 加珠子（特任准教授）

1

樺山 一哉（准教授） , 真鍋 良幸（助教） , 下山 敦史（助教） , 白神 宜史（特任准教授） ,3
3
中崎 有恒（技術研究所所長） , 釜堀 香織（事業開発部マネジャー）
2

2

2

1

		1 放射線科学基盤機構
		2 理学研究科
		3 株式会社カイオムバイオサイエンス
配分額

400,000 円

実績額

400,000 円

日本初の放射線医薬であるゼヴァリンの開発に関わっていたメンバーを有するカイオムバイオサイエンス株式会社（以下 C 社）は、他企業に比べて放射線医薬に対する理解が深いことが期待された。そこで、C 社の持つ特殊抗体作製技術を応用し「Tribody 技術を用いて pre-targeting を検討する」というテーマを、共同研究プロジェ

クトとして立ち上げるべく、準備を進めた。しかしながら、本事業により共同研究の具体的実施に向けた検討会を重ねる中で、我々が思っていた以上に問題が山積していることが明らかとなった。
まず、プロジェクトの推進に先立ち、C 社の持つ独自のライブラリの中より、我々の成果を踏まえた核医学治療薬に好ましい条件を持つ抗体の選抜を進めた。しかしながら、調査の結果、開発の進んでいる抗体はすでに単独で効能を示しており、供給に係る経費の面でも知的財産権の問題からも、核医学治療薬の原料として阪大へ供給することは極めて困難であることが明らかとなった。また、供給を行う際には、知的財産権の所在を明らかにし、場合によっては C 社以外との契約も必要であることが明らかとなった（例えば C 社が阪大以外のア

カデミアと共同開発している抗体は、権利は阪大以外のアカデミアにもあり、その許可を取らずに阪大に勝手に供給するわけにはいかない）。一方で副作用を低減する核医学治療薬の開発には、改めて C 社の保有している抗体エンジニアリング技術である多重特異性抗体 Tribody 技術を利用することが最も効果的であると考えられた。しかしながら、当機構において、現時点では明らかな標的分子を決定できておらず、標的の選定を C 社に頼るには限界がある。Tribody による pre-targeting を行うための最適な標的の選抜、具体的な抗体のデザインに関して継続した情報収集を行うことが必要である。また、知的財産権の面での問題を解決するためには、
抗体開発の段階からの共同研究という形をとることが望ましいことが確認された。一方、放射線科学基盤機構/ 理学研究科では電気分解による抗体標識技術の開発を進めている。本技術が成功すれば、キャリア不要且つ簡便な標識が可能となる。しかしながら現時点では、当技術はトライアルの状態であり、当機構側から C 社にIII提供できるものがないという状況もある。

Achievements

知財の面においては、会社対アカデミアで行うよりも、会社対会社で行う方が簡便且つ問題が少ないことも明らかとなった。現在、参画者である白神を代表とするベンチャー設立支援のグラントを受けており、知財の取り扱いに関しては、新規ベンチャーを介することで問題の回避が可能であると考えられた。本プロジェクトにおいては、年内までは C 社が阪大に来訪してミーティング、年明けからは阪大から C 社へ向かうことを計画していたが（抗体製造現場の見学）、COVID-19 のため、お互いの行き来の制限が生じたため、電話会議および Web ミーティングを実施した。

現時点で共同研究契約には至らなかったのは残念ではあったが、C 社とのブレインストーミングは非常に意義のあるものであった。

IRS ANNUAL REPORT

2018-201964

BNCT のための

小型の中性子発生装置の開発
代表者
参画研究者

村上 秀明（教授）1村上 匡且（教授） , 内山 百夏（助教） , 岩本 悠里（医員） , 眞嶋 みなみ（大学院生）
2

1

3

1

		1 大学院歯学研究科 歯科放射線学教室
		2 レーザー科学研究所
		3 歯学部附属病院 放射線科
配分額

500,000 円

実績額

500 000 円

私達の研究のゴールは、車で持ち運びできる程度の大きさまでダウンサイズした中性子発生装置を開発し、各所で BNCT を行うことであるが、本申請期間内での研究プロジェクトの目的は、国内外の中性子発生装置とこれを用いた最新研究の調査と、α線を用いた放射線治療の動向、頭頸部癌における BNCT 治療の動向を検討することである。そして、私達が提案する BNCT が実現するような、分野横断的な研究組織の構築を意図した

ワークショップ開催することを目的とした。

まず、研究者の村上匡且は、2019 年 11 月に台湾で開かれた第 3 回アジアオセアニア中性子学会に参加し、特に BNCT 治療の動向を調査した。その結果、BNCT 治療は現在は施設の問題でほとんど行われていないことが判明し、さらには小型の中性子発生装置の開発に関する研究は皆無であった。さらに村上匡且は、1 編の英語論文「Generation of quasi-monoenergetic ions using optimized hollow nanospheres. Physics ofPlasmas，27, 033103 (2020)」、1 辺の日本語総説「マイクロバブル爆縮による超高場の生成と相対論的プロトン放射 . Journal of Plasma and Fusion Research，Vol.95, No.10」、7 編の proceeding を含む 15 本の学会発表を行った。

続いて、研究代表者の村上秀明は、2019 年 12 月に福岡で開かれた第 24 回臨床画像大会で教育講演「α線を用いた放射線治療」を行い、同名タイトルで総説を執筆した。また、医歯薬出版から「歯科放射線学・第 6 版」

を分担執筆し、『放射線治療の概念と治療機器』の事項を担当した。また、同じく医歯薬出版から「口腔外科学・第４版」の教科書において、『放射線療法』の事項を担当し、特にα線を用いた放射線治療関して記載した。また、
大阪府保険医新聞に４回連載で放射線の有効利用について寄稿した。さらに、耳鼻咽喉科・頭頸部外科雑誌の91 巻にて、放射線治療のひとつである小線源療法について著した。また、2019 年 12 月に中国・北京で開かれた中日医学フォーラムに招待され、放射線治療についての招待講演を行った。

III
Achievements

続いて、2 つの学会に参加し、ワークショップを開催する準備を進めていたが、COVID-19 の影響で全てが中止となった。

このため、予定を変更し、これまでのα線を用いた放射線治療と BNCT 治療に関する清書を購入し、次年度のワークショップ開催に向けて、オフィス環境を整備した。

65

IRS ANNUAL REPORT

2018-2019

加速器 RI 応用研究を推進する
大規模製造の分野横断的連携体制の構築
代表者
参画研究者

豊嶋 厚史（特任教授）

1

吉村 崇（教授） , 篠原 厚（教授） , 笠松 良崇（講師） , 寺本 高啓（特任研究員） ,4567
羽場 宏光（チームリーダー） , 菊永 英寿（准教授） , 塚田 和明（主席研究員） , 石岡 典子（部長）
2

3

3

1

		1 大阪大学放射線科学基盤機構
2 大阪大学放射線科学基盤機構附属 RI センター
3 大阪大学理学研究科
4 理化学研究所仁科加速器研究センター
5 東北大学電子光理学研究所
6 日本原子力研究開発機構先端基礎研究センター
7 量子科学技術研究開発機構高崎量子応用研究所
配分額

478,000 円

実績額

0円

本申請では、我が国の加速器施設において RI 製造を行っているグループを集結し、RI 製造のコア体制を整える。各グループが持つ RI 製造の知識や技術を共有化し、大規模製造技術の開発へと発展させる。また、放射線防護など関連する研究分野との連携体制を構築する。具体的には、定期的な研究会の開催、国内外での情報収集、大規模製造のための研究体制構築、試験実施のための研究費獲得、専用製造施設の構想などを行う。将来的には大規模製造技術を完成させ、新たな RI 利用研究を促進する。
本年度、まずは RI 製造のコア体制を整えるべく、3 月 19-20 日に開催予定であった機構シンポジウム / ワー

クショップ「Theranostics from radioisotope production technology to clinical application において、加速器 RI 製造や分離のセッションを準備していた。本研究グループのメンバーほぼ全員による招待講演を行い、さらにサテライト的にミーティングを行う事を想定していた。しかしながら、新型コロナウイルスの影響のため、機構シンポジウム / ワークショップ自体が延期となってしまい、同様に研究グループミーティングも行えなかった。

しかしながら、本申請経費はすべて令和 2 年度に繰り越しており、国内外の状況が改善次第、機構シンポジ

ウムを行うと共にミーティングを行いたい。また、現在の状況を鑑みて、Web ミーティングの開催も考慮したいと考えている。

III
Achievements

IRS ANNUAL REPORT

2018-201966

核医学治療の最適化をめざす
分野横断的研究体制の構築
代表者
参画研究者

米倉 義晴（特任教授）

1

畑澤 順（特任教授） , 篠原 厚（教授） , 深瀬 浩一（教授） , 吉村 崇（教授） , 高橋 成人（特任教授） ,4566中島 裕夫（助教） , 巽 光朗（副部長） , 加藤 弘樹（講師） , 渡部 直史（助教） ,2447佐藤 達彦（特任教授） , 兼田 加珠子（特任准教授） , 白神 宜史（特任准教授） , 真鍋 勇一郎（助教） ,89和田 隆宏（教授） , 手島 昭樹（主任部長）
2

3

3

4

2

		1 放射線科学基盤機構 放射線科学部門
		2 核物理研究センター
		3 理学研究科
		 4 放射線科学基盤機構
		 5 医学部附属病院放射線部
		 6 医学部核医学講座
		 7 工学研究科
		 8 関西大学システム理工学部
		 9 大阪国際がんセンター放射線腫瘍科
配分額

475,000 円

実績額

375,000 円

放射性核種を体内に投与する核医学治療では、標的となるがん細胞に対して十分な線量を照射するとともに、正常組織への影響を考慮した治療計画が重要である。特にアルファ線核種など生物作用の強い高 LET 放射線を利用する治療では、治療患者ごとの適切な線量評価と生物学的影響の評価が不可欠と考えられるが、その手法は未だ確立されていない。本研究プロジェクトでは、核医学治療における治療の最適化を目指して、物理的線量評価と生物学的評価を統合的に扱うために、医学、生物学、物理学、化学などの専門家が分野を超えて協力できる新たな研究体制を大阪大学に構築する。
核医学治療における治療効果の最適化を目指す分野横断的研究体制を構築することを目的として、学内外の専門家と研究者を中心に「大阪大学核医学治療研究会」を発足させ（参加者 20 名）、これまでに 4 回の研究会を開催した。

• 第 1 回（11/25）「研究会の設立（米倉）と基調講演（畑澤）」（出席者 13 名）• 第 2 回（12/20）「α線核医学治療研究の概要（白神）」（出席者 11 名）• 第 3 回（1/17）「がん特異的 PET イメージングからアルファ線治療への展開（渡部）」（出席者 13 名）• 第 4 回（2/10）「放射線による細胞障害の線質差（兼田）・線量・生存率グラフに肩がある意味とIII

治療上の利点・不利点（中島）」（出席者 13 名）

Achievements

学内の研究者から核医学治療に関する研究概要の説明を受けて、それぞれの研究者の抱えている問題点を洗い出し、解決すべき課題の抽出とその方法について議論を深めた。その中で、標識化合物の体内動態（ミクロを含む）、内部被ばくの線量評価と線量率効果、アルファ核種による生物影響、などの課題が抽出されてきた。
これらの課題に対して、外部の専門家との意見交換を実施することとした。低線量率放射線の影響研究を進めている環境科学技術研究所（青森県）を訪問し、核医学治療への応用を目指す研究方法について意見交換を行った。アルファ核種などの内部被ばくによる生物影響の評価については、ターゲットとする生物影響の指標を含めて、標準的な測定法を確立することが重要との結論を得た。一方、アルファ核種の内部被ばくによる生物影響については、過去に造影剤として利用されたトロトラストの影響を調べている福本学博士（東北大学名
誉教授）の講演と意見交換を予定したが、新型コロナウイルスの感染拡大の影響を受けて講演会を延期せざるを得なくなり、予定を次年度に持ち越した。
今回発足した大阪大学核医学治療研究会は、学内外の共同研究を推進するための情報共有と議論の場として積極的に活用していく予定である。今後、これまでに明らかになった研究課題について、さらに議論を深めて新たな研究費の獲得につなげていく。

67

IRS ANNUAL REPORT

2018-2019

NAME INDEXNameA ADACHI, Sadia

Name

N NAKAJIMA, Akihisa

39

NAKAJIMA, Hiroo27, 28, 43, 52, 53, 67

ASAI, Masato

31, 43, 44

NAKANO, Takashi

16, 5331

28

NANJO, Hajime

35, 37, 47

FUKASE, Koichi

5, 15, 16, 20, 46, 53, 55, 67

NINOMIYA, Kazuhiko36, 46, 47

FUKUDA, Mitsuhiro

6, 10, 16, 19, 23, 47, 53, 54,
56, 57NISHIZUKA, Kaito

31

NOMACHI, Masaharu

7

G GIESEL, Frederik L.
H HABA, Hiromitsu

5, 6, 25, 47, 54, 56
10, 31, 33, 43, 44, 46, 53, 54,
56, 62, 66

HABERKORN, Uwe

6, 25, 56

HASHIMOTO, Taichi

40

HATAZAWA, Jun

6, 16, 18, 23, 25, 47, 48, 53,
54, 56, 57, 67

HAYAMI, Sho

33, 46

HIROSE, Minoru

35

HUANG, Xuhao

15

ICHIMURA, Soichiro

6, 19, 21, 44, 56, 57

IGARASHI, Jyunya

36, 46

IWAMOTO, Yuri

38, 49, 57, 58, 62, 65

IZUMI, Yoshinobu

30, 43

K KABAYAMA, Kazuya

O OBATA, Honoka

15, 16, 20, 46, 53, 55, 64

KADONAGA, Yuichiro

5, 15

KAJIWARA, Tomohiro

36, 46KANAI, Yoshikatsu

16, 48KANDA, Akimitsu

19, 21
46, 47, 53, 54, 55, 56, 57, 62,
64, 67KASAMATSU, Yoshitaka

31, 33, 46, 66

KASHIHARA, Ayuna

31

KATO, Mizuho

31

KIKUNAGA, Hidetoshi

10, 24, 44, 53, 54, 56, 62, 66

KINO, Yasushi

12, 32, 44

KOMORI, Yukiko

31, 43, 44

KON, Yukiyoshi

9, 19

KRATOCHWIL, Clemens

24, 25

KUSAKA, Sachie

39, 40LINDNER, Thomas
LIU, Yuwei

M MANABE, Yoshiyuki

3

OKADA, Michio

29, 43, 52

OKITA, Akiko K.

34, 46

OOE, Kazuhiro

6, 16, 17, 18, 19, 21, 22, 23,
25, 43, 44, 47, 53, 54, 56, 57,
62
39, 40SEKINE, Tsutomu

12, 32, 44

SHIGEKAWA, Yudai

31, 33, 43, 45

SHIMIZU, Kikuo

30, 43SHIMOSEGAWA, Eku

6, 18, 23, 25, 47, 48, 54, 57

SHIMOYAMA, Atsushi

15, 16, 19, 46, 53, 55, 64

SHINOHARA, Atsushi

6, 12, 16, 17, 18, 19, 20, 21,
22, 23, 25, 32, 33, 34, 44, 46,
47, 48, 53, 54, 55, 56, 57, 62,
66, 67SHIRAKAMI, Yoshifumi

5, 6, 16, 18, 23, 25, 46, 47,
53, 54, 56, 57, 64, 67

SHIRASAKI, Kenji

17, 24, 53, 54, 56, 62

SUEKI, Keisuke

31

SUZUKI, Tomokazu

9, 10, 54, 55, 62

SUZUKI, Yusuke

31

T TAKAYAMA, Tsutomu

12, 32, 44

TAMAKI, Shingo

32, 33TERAMOTO, Takahiro

5, 19, 21, 22, 53, 56, 66

TOKOI, Katsuyuki

31, 44TONAI, Katsuma

33

TOYOSHIMA, Atsushi

5, 6, 16, 17, 18, 19, 20, 21,
22, 23, 24, 25, 31, 43, 44, 46,
47, 52, 53, 54, 55, 56, 57, 62,
66

6, 25, 56

TSUJIMOTO, Tomomi

38, 49, 62

6, 18, 23, 25, 47, 54, 56, 57

TSUKADA, Kazuaki

24, 31, 43, 44, 66

15, 16, 20, 46, 53, 55, 64

MARUTANI, Keisuke

38, 49

MATSUDA, Masaya

36

MATUO, Youichirou

30, 43MIYAMARU, Hiroyuki

40

MORI, Daiki

31

MURAKAMI, Shumei

38, 48, 49, 52, 57, 58, 62, 65

MURATA, Isao39, 40N NAGATA, Kojiro

6, 19, 21, 22, 44, 56, 57

OGAWA, Tetsuo

S SATO, Fuminobu

KANEDA-NAKASHIMA, Kazuko 5, 6, 16, 18, 20, 23, 25, 43,

L

Page

ANGXUAN, Jiang

F FUJIWARA, Tomoko

I

Page

31

6, 11, 12, 17, 19, 21, 24, 25,
32, 44, 53, 54, 55, 56, 57, 62

NAKAGAWA, Sota

19, 21, 56

NAKAGAWA, Takuro

34, 46W WANG, YangY31

WATABE, Tadashi

6, 16, 18, 23, 25, 46, 47, 48,
52, 53, 54, 56, 57, 62, 67

WATANABE, Eisuke

33, 46YAMAGUCHI, Yoshiaki

11, 36, 46, 53

YAMAGUCHI, Miyabi

30

YAMANAKA, Taku

37, 47, 56

YOKOKITA, Takuya

31, 33, 16

YOSHIMURA, Takashi

6, 9, 10, 11, 12, 16, 17, 19,
21, 22, 32, 44, 46, 47, 53, 54,
55, 56, 57, 62

Z ZHANG, Zijian

6, 15, 36, 44, 46, 53, 54, 55,
56, 57, 62

IRS ANNUAL REPORT

2018-201968

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