NCT letter Vol. 6（English version）
May, 2020

NCT letter Issue 6 June 2019

Contents● Preface
Hiroyuki Nakamura
President of Japanese Society of Neutron Capture Therapy
Professor of the Institute of Innovative Research, Tokyo Institute of Technology● Special Articles
・Encounter with BNCT and wishes
Akira Maruhashi
Professor, Institute for Integrated Radiation and Nuclear Science, Kyoto University

・BNCT and PET
Jun Hatazawa
Professor, Research Center for Nuclear Physics, Osaka University

・BNCT & International Atomic Energy Agency(IAEA) activity
Kazuyo Igawa
Associate Professor, Neutron Therapy Research Center, Okayama University● Academic meeting Reports
・Report on the 15th Japanese Congress on Neutron Capture Therapy
President Masayori Ishikawa
Professor, Graduate School of Health Sciences, Hokkaido University

・Report on the 18th ICNCT (Taipei)
Hiroaki Kumada
Associate professor, University of Tsukuba Faculty of Medicine, Proton Medical
Research Center・Report of BNCT session at AACR (American Association of Cancer
1NCT letter Issue 6 June 2019

Research), 2019
Akira Matsumura
Professor, Department of Neurosurgery, University of Tsukuba Hospital・Notice on the 10th Young member’s BNCT Meeting (YBNCT 10)
President

Hanna Koivunoro

Medical Physicist at Neutron Therapeutics Inc. Finland・Notice on the 15th Japanese Congress on Neutron Capture Therapy
President

Minoru Suzuki

Professor, Institute for Integrated Radiation and Nuclear Science, Kyoto University

・Notice on the 19th ICNCT (Granada)
President

Ignacio Porras

Departamento de Física Atómica, Molecular y Nuclear, Facultad deCiencias, Universidad de Granada● Awardees of BNCT related Conferences or Meetings
Best Presentation Awards of 15th Japanese Congress on Neutron
Capture Therapy
・Development of the cylindrical neutron spectrometer for acceleratorbased BNCT irradiation field.
Kentaro Baba
Graduate School of Biomedical Science and Engineering, Hokkaido University

・Enhancing therapeutic potential of boronophenylalanine by controllingits metabolism using biocompatible polymers
Takahiro Nomoto, et al,
1

Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo
Institute of Technology

・Development of neutron capture therapy using boron-binding adenovirus
vector2

NCT letter Issue 6 June 2019

Sayuru Tsuyuguchi, MD
Department of Neurosurgery, Graduated School of Biomedical and Health Sciences,
Hiroshima University

Awardees of 18th International Congress on Neutron Capture Therapy
・In receiving the Special Award, Global Outstanding Achievement Award
Koji Ono
Director of Kansai BNCT Medical Center, Osaka Medical College
・On receiving the Hatanaka Award
Mitsunori Kirihata
Professor, Laboratory for Medicinal Chemistry for Boron Drug, Research Center
for BNCT,
Organization for Research Promotion, Osaka Prefecture University

・On receiving the Hatanaka Award
Junichi Hiratsuka
Professor, Department of Radiation Oncology, Kawasaki Medical School
The Fairchild Award
・Collimator Design of T/N-SPECT for BNCT
Saki Shibata
Division of Sustainable Energy and Environmental Engineering, Graduate School ofEngineering, Osaka University

・Development of a prompt gamma ray imaging detector using LaBr3(Ce)scintillator and arrayed MPPC for boron neutron capture therapy
Keita Okazaki, et al.
Graduate School of Engineering, Kyoto University

・ Neutron beam quality measurement of an accelerator-based neutron
source using microdosimetric technique
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NCT letter Issue 6 June 2019

Naonori KO, et al.
Graduate School of Engineering, Kyoto University● Introduction of the articles
1. <Biology >Title: Eosinophil depletion suppresses radiation-induced small intestinal fibrosis
Authors: Naoki Takemura, Yosuke Kurashima, et al.
The source: Science Translational Medicine, 2018 Feb 21; 10(429)https://stm.sciencemag.org/content/10/429/eaan0333/tab-pdf
Presented by Lichao Chen (Department of Frontier Life Sciences, Nagasaki
University Graduate School of Biomedical Sciences)
2. <Medicine >Title: Boron neutron capture therapy for high-grade skull-base meningioma
Authors: Koji Takeuchi, Shinji Kawabata, et al.
The source: Physics in Medicine & Biology (2017) 62: 4421-4439
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133692/
Presented by Yusuke Fukuo (Department of Neurosurgery and neurovasculartherapy, Osaka Medical College Hospital)
3. <Physics>
Title: Fast neutron dose evaluation in BNCT with Fricke gel layer detectors
Authors: G. Gambarini, G. Bartesaghi, et al.
Radiation Measurements 45 (2016) 1398-1401
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100278/
Presented by Yuto Murakami, et al (Graduate School of Engineering, Hiroshima
University)
4. <Pharmacology>
Title: Design, synthesis, and evaluation of lipopeptide conjugates of mercaptoundecahydrododecaborate for boron neutron capture therapy
Authors: Aoi Isono, Mieko Tsuji, et al.
The sources: ChemMedChem (2019) 14 : 823-832
https://chemistry-europe-onlinelibrary-wiley-com.remote.library.osaka4

NCT letter Issue 6 June 2019u.ac.jp:8443/doi/full/10.1002/cmdc.201800793
Presented by Kazuki Kawai (Laboratory for Chemistry and Life Science Institute of
Innovation Research, Tokyo Institute of Technology)● Editorial Postscript
Itsuro Kato
Chief Editor of NCT letter
Department of Oral and Maxillofacial Surgery II, Graduate School of Dentistry, Osaka
University

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NCT letter Issue 6 June 2019

On the occasion of the publication of NCT letter
issue No.6
Hiroyuki Nakamura
President, Japanese Society of Neutron Capture Therapy
Professor, Institute of Innovative Research, Tokyo Institute of Technology
Thanks to the efforts of the editor-in-chief Dr. Itsuro Kato and through cooperation withour colleagues, the sixth issue of NCT letter was successfully published. I take thisopportunity to express my sincere gratitude to them.
In this issue, we asked three professors to write feature articles: Dr. Akira Maruhashi(Professor Emeritus, Kyoto University) who contributed greatly to the development of
the world's first accelerator for BNCT, Dr. Jun Hatazawa (Professor Emeritus, Osaka
University) who expressed his own research activity including 18F-BPA PET imaging
study, and Dr. Kazuyo Igawa (Associate Professor, Okayama University) who plays anactive role as a pipe between the International Atomic Energy Agency (IAEA) and theInternational Society of Neutron Capture Therapy (ISNCT).
At the 18th International Congress on Neutron Capture Therapy (ICNCT18) held in
Taipei last October, Prof. Koji Ono, the first president of the Japanese Society of
Neutron Capture Therapy (JSNCT), received the Global Outstanding Achievement
Award, and Prof. Mitsunori Kirihata, the second president of JSNCT, and Prof. Junichi
Hiratsuka, the third president of JSNCT, received the Hatanaka Prize. In addition, Dr.
Saki Shibata, Dr. Keita Okazaki, and Dr. Naonori Ko, received the Fairchild Award.
These awards are very prestigious to JSNCT.
At the 15th Annual Meeting of the Japanese Society for Neutron Capture Therapy heldin Hokkaido University in September last year, Dr. Kentaro Baba, Dr. Takahiro
Nomoto, and Dr. Atsushi Tsuyuguchi received the Best Presentation Award. I wish tocongratulate the award-winning members and wish them further progress and success inthe future.
As you know, the Phase II clinical trial for the world's first accelerator neutron source forbrain tumors and head and neck cancer that started in 2012 has been completed and is
now under preparation for approval. In addition, the Phase II clinical trials for malignant
meningiomas at Osaka Medical College and for malignant melanoma and angiosarcoma
at National Cancer Center Hospital have commenced. Now, BNCT in Japan is facing a
critical moment for the realization of “Treatment for Patients” ahead of the rest of theworld. I hope that the members of JSNCT will work together so that many patients can
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NCT letter Issue 6 June 2019

receive BNCT as soon as possible.
Thank you for your continued support and understanding.

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NCT letter Issue 6 June 2019

Encounter with BNCT and wishes
Akira Maruhashi
Professor, Institute for Integrated Radiation and
Nuclear Science, Kyoto University
1 Encounter with BNCTIn July 2002, I joined the Kyoto University Research Reactor Institute (renamed Kyoto
University Institute for Integrated Radiation and Nuclear Science-KURNS in 2018) withthe dream of building a proton therapy facility here. However, my feelings changed
completely after witnessing the treatment of BNCT parotid gland cancer with epithermal
neutrons, which was first attempted at KURNS in December 2001. I was truly shocked!
I engaged in the endeavor of proving the clinical effectiveness of BNCT.
2 Kyoto Univ. Reactor Based Thermal- & Epithermal- Neutron BNCTIn March 2003, we started an annual plan review meeting mainly with doctors from the
Department of Radiology at Kawasaki Medical School, Osaka University School of
Dentistry, and Osaka Medical College Department of Neurosurgery, and a “clinicalresearch implementation plan” was established, under the direction of Prof. Ono, to
confirm the actual clinical evaluation of BNCT. A joint research system was organized
mainly with the doctors mentioned above and the doctors from Osaka Prefectural
University in the Research Department of BPA, in order to evaluate the effectiveness of
BNCT. The main research subjects for about 3 years until 2005 were brain tumor, headand neck cancer, liver tumor, malignant melanoma, mesothelioma and lung cancer.
During this period, the number of BNCT patients reached about 180. At that time, thesituation was changing on the premise of the disposal of KUR. However, requests forcontinued use of KUR, including those from people involved with BNCT, were greatly
approved. KUR-BNCT has been suspended for a while due to the Great East Japan
Earthquake in March 2011, but is now operating smoothly.
3
Accelerator Based Epithermal Neutron BNCTAs mentioned above, when the possibility of reactor decommissioning was raised as arealistic issue, BNCT promoters were required to present and develop policies for futureissues, taking into account the progress of research and the perspective of disseminating
BNCT. A wide variety of accelerators has already been proposed mainly in Europe as
neutron sources for NCT. In Japan, many of them were using a reaction between 2-3 MeV
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NCT letter Issue 6 June 2019

protons and Li. This energy selection is presumed to be based on the understanding that
NCT is based on thermal neutron irradiation (with a treatable depth of about 2.5 cm),
assuming that there is a high probability of failure of fast neutrons. The main treatment
targets for NCT were refractory Glioblastoma Multiforme (GBM) and malignant
melanoma. In the case of GBM, which is a deep cancer, after surgery to remove the centerof the lesion at the patient's main hospital, treatment was resumed at the reactor irradiation
field operation site, and irradiation was performed with reduced depth. It seems that theaccelerator’s neutron generation system was devised along this flow. At the time of myprevious job at the University of Tsukuba, I designed an irradiation system and shielding
system for fast neutron radiation therapy using a neutron beam with an average energy of
70 MeV generated by 500 MeV protons, and worked to explore the possibility of its use
for medical treatment. Based on experience including animal experiments using theMedical Science Institute's cyclotron neutrons, even in the FFAG accelerator utilization
plan, it is relatively easy to operate the neutron generation system including the target.
Therefore, I planned a proton beam and neutron generation target system of about 20 MeV,on the premise of maintaining homeostasis, important for medical treatment. In late 2005,
I started negotiations with accelerator manufacturers based on this experience. In late2006, a contract was signed with Stella Chemifa Corporation and Sumitomo Heavy
Industries, Ltd. for a proton accelerator and neutron irradiation system (30MeV proton
accelerator cyclotron) to be developed and installed in the medical building. Design
production and joint research started in early 2007. This was made possible by Prof. Ono's
efforts to provide the medical building with a budget for the development, production,and medical research of the BNCT accelerator neutron source and irradiation system. In
May 2006, Mr. Hiroki Tanaka, currently associate professor, joined the research team andstarted to design and produce a neutron moderator and epithermal neutron irradiation
facility. A facility approval certificate based on the Radiation Hazard Prevention Act wasissued on February 28, 2008, and installation adjustment of the accelerator system to the
medical building was started from the latter half of the year. On January 29, 2009, thebeam trial operation started, and various rating measurements were carried out. A passing
certificate was issued on March 31 of that year, and the Cyclotron Based Epithermal
Neutron Source (C-BENS) operation started. From April, in order to verify the effects ofirradiation, various tests were conducted, such as measurements in BNCT irradiation field,
radiation fields inside and outside the facility, and animal irradiation experiments. In
March 2014, a clinical trial of accelerator BNCT was started at this facility. In addition,a facility with BNCT accelerator irradiation equipment of the same standard as KURN’s
was constructed in Southern Tohoku Hospital in Koriyama City, Fukushima Prefecture,9

NCT letter Issue 6 June 2019

in relation to reconstruction after the Great East Japan Earthquake. A clinical trial was
conducted in collaboration with this facility, and in June last year, trials were completed
for as many cases as needed to obtain national policy on brain tumors and head and neckcancer. In addition, a BNCT accelerator irradiation facility with the same standards as
KURN’s at Osaka Medical University, which had been under construction for two years,
was completed in March. Preparatory work for clinical trial research has been carried out,
and I am participating in basic research issues.
4 Wishes
My life at the Institute since 2002 has been completely immersed in BNCT. I am gratefulfor this wonderful environment. I believe that BNCT can be the ultimate weapon against
multiple cancers.
Wishes concerning this BNCT:① Current epithermal neutrons have a therapeutic depth of up to approximately 6 cm,
and the whole body, especially the abdominal region such as the liver, is outside the portal(Evaluation of self-absorption is important for increasing the concentration of 10B incancer tissue). Let us break this limit! Deepening of the thermal neutron distribution (withan increase in the fast neutron component) is considered inevitable, and the introductionof gantry multidirectional irradiation is a prerequisite.
② Building an accelerator BNCT medical facility in Kumatori town, establishing a
joint research system with the KURNS accelerator facility, creating a research and clinicalmutual prosperity system, and leading the battle against cancer.

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NCT letter Issue 6 June 2019

BNCT and PET
Jun Hatazawa
Professor, Research Center for Nuclear Physics, Osaka
University
In March of this year (2019), I retired from professor at the
Department of Integrated Radiation Medicine (Nuclear Medicine), Graduate School of
Medicine, Osaka University. I gained a lot of experience and had a fulfilling time. Thanks
to the warm guidance and support of the teachers at the faculty, I was able to complete
successfully my 17-year term.
I express my heartfelt gratitude. From April, I was
assigned to the Research Center for Nuclear Physics, Osaka University where I continue
my research toward new goals. I look forward to your continued guidance.
Nuclear medicine is a field that applies the power of atoms to medicine. Diagnostic
imaging Image with γ-rays and positrons, and treatment with β-rays and α-rays are being
carried out, and nuclear medicine practice is changing dramatically due to improved
performance of imaging devices and the development of new radionuclide-labeled drugs.
Among that, boron neutron capture therapy (BNCT) is considered to be a nuclear
medicine treatment because the cell killing effect depends on the amount of radioisotopes
produced in the tissue. The absorbed dose depends on the accumulation of 10B
administered intravenously, and the accumulated amount can be measured with PET. The
PET micro-dose test method can be applied to develop a boron carrier with higher tumor
accumulation.
After graduating from Tohoku University in 1979, I entered the doctoral program of
Tohoku University Graduate School of Medicine and belonged to Department ofRadiology, Research Institute for Tuberculosis and Cancer (Prof. Taiju Matsuzawa). My
mentor was Dr. Hiroshi Fukuda, four years my senior (at that time, assistant Professor).
Dr. Fukuda had been visiting Kansai several times a year for group meetings andexperiments of the Mishima group. I remember that he was conducting irradiation
experiments on cultured cells. At Matsuzawa Lab, he was working on the developmentof radiology using particle beams (such as proton radiography, PET, and PIXIE).
Prof. Tatsuo Ido, famous for the development of FDG, had a laboratory at the Cyclotron
and Radioisotope Center, Tohoku University in Aobayama Campus, and in the mid 1980s,
11NCT letter Issue 6 June 2019

Dr. Yoshio Imahori enrolled at Department of Neurosurgery, Kyoto Prefectural Universityof Medicine. At that time, I think I heard the term boron neutron capture therapy for the
first time. Research on BPA labeled with 18F began by Dr. Fukuda's idea. Dr. Kiichi
Ishiwata succeeded painstakingly in 18F-BPA synthesis. Since then, biodistribution has
been experimented. Dr. Imahori (who returned to Kyoto Prefectural University of
Medicine) and his research group conducted the clinical study of 18F-BPA PET actively
at Nishijin Hospital in Kyoto.
Around 2006, Prof. Hiroshi Fukuda of Tohoku University and Prof. Junichi Hiratsuka of
Kawasaki Medical School visited the laboratory at Osaka University, and suggested theidea of starting a 18F-BPA PET at Osaka University. Since I was assigned to Osaka
University in 2002 and was working on the development of the laboratory, it took time tostart. However, with Dr. Yasukazu Kanai (currently at Kansai BNCT Medical Center,
Osaka Medical College), responsible for the radiolabeling synthesis, Dr. Kohei Hanaoka(currently at the Radiology Department, Kindai University Hospital), in charge of basic
research, and Dr. Kayako Isohashi (currently at Kansai BNCT Medical Center, Osaka
Medical College), in charge of the clinic, the 18F-BPA PET started at Osaka University.
Prof. Eku Shimosegawa (Dept. of Molecular Imaging in Medicine) evaluated thesystemic distribution in healthy subjects and found that 18F-BPA is rapidly excreted fromnormal organs and that accumulation is low (2016). We have also developed a method for
estimating the BPA concentration in tissues when a therapeutic amount of BPA isadministered based on 18F-BPA PET. Dr. Hanaoka prepared a cell culture experimental
environment and reported that the accumulation of tracer amount of 18F-BPA andtherapeutic amount of BPA are equivalent (2014). Dr. Isohashi measured changes overtime in 18F-BPA concentrations in tumor tissue and blood (2016). Dr. Tadashi Watabe(Nuclear Medicine) discovered that 18F-BPA is specifically taken up by tumor cells via
L-type amino acid transporter 1 (LAT1) (2017). Since LAT1 was known to appear inmany human cancer cells, it was found that BNCT by BPA could be used to treat many
major malignancies in Humans. At the same time, we understood through 18F-BPA PET
that, that itself could be a malignant tumor specific testing method. Dr. Roua’a Beshr, a
PhD student from Yemen, reported that 18F-BPA is highly accumulated in recurrent brain
tumors and low in radiation necrosis (2018). Dr. Victor Romanov, a PhD student from
Russia, analyzed the 18F-BPA accumulation quantitatively with compartment model(2019).
What 18F-BPA PET has to overcome is the yield of 18F-BPA. With conventional methods,
only two people's PET examination is possible with one radiolabel synthesis. Currently,
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NCT letter Issue 6 June 2019the research team of Prof. Mitsunori Kirihata at Osaka Prefectural University is actively
working on the development of a new radiolabel synthesis method, and expectations are
high.
In Kansai, many years of BNCT basic research and clinical research have been
accumulated using a nuclear reactor as a neutron source (Prof. Koji Ono, Prof. Maruhashi,
Prof. Minoru Suzuki). The Kyoto University Institute for Integrated Radiation and
Nuclear Science (leading the world's BNCT medicine), the Osaka Prefectural University(conducting Boron carrier Research), and the Osaka University Mirai Medical Imaging
Center are working closely together to promote research in this field. In 2018, the Osaka
Medical University BNCT Center, the clinical center of accelerator BNCT, was opened(Director Koji Ono). The second phase of the world's first BNCT clinical trial has been
completed at the Institute for Integrated Radiation and Nuclear Science, Kyoto University
and the Southern Tohoku General Hospital, and preparations are now underway for theapproval of the Pharmacopoeia Act. I heard that the National Cancer Center started aclinical trial. In the future, I hope that the PET method can contribute to the selection of
BNCT adaptation examples, the evaluation of therapeutic effects, and the development of
new boron carriers.

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NCT letter Issue 6 June 2019

Boron Neutron Capture Therapy (BNCT) andInternational Atomic Energy Agency (IAEA) activity
Kazuyo Igawa
Associate Professor, Neutron Therapy Research Center
Okayama University
Outline of IAEA
In 1953, U.S. president Eisenhower proposed ‘Atom for Peace’ and the International
Atomic Energy Agency (IAEA) was established as autonomous organization in 1957. In
2009, Yukiya Amano of Japan was elected as the Director General (DG) for the IAEA andhave achieved the goal ‘Atoms for Peace and Development’ (Fig.1). After DG. Amano’s
death in July 2019, Rafael
Mariano Grossi of Argentina was
appointed as DG in Oct. 28th
2019. The objective of IAEA is‘…seek to accelerate and enlarge
the contribution of atomic energy
to peace, health and prosperity
throughout the world’ and ‘…ensure, so far it is able, that assistance provided by it or at
its request or under its supervision or control is not used in such a way as to further
military purpose. [1] The three main mission of IAEA is Peaceful uses, Safeguards andNuclear safety and the main function is General Conference, Board of Governors andSecretariat. IAEA consists of 6 departments such as Management (MT), TechnicalCooperation (TC), Nuclear Energy (NE), Nuclear Safety and Security (NS), Nuclear
Sciences and Applications (NA) and Safeguard (SG).
BNCT at IAEA
In 1959, Point 2 Article 1 of Agreement between the World Health Organization (WHO)and IAEA states that “…it is recognized by WHO that IAEA has the primary
responsibility for encouraging, assisting co-ordinating research on, and development andpractical application of, atomic energy for peaceful uses throughout the world without
prejudice to the right of WHO to concern itself with promoting, developing, assisting andco-ordinating international health work, including research, in all its aspects [2]. This thereason why IAEA is fulfilling the mission on health consequences of radioactivity,
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NCT letter Issue 6 June 2019

including Boron Neutron Capture
Therapy (BNCT). BNCT isrelated with department of
NuclearSciences
andApplications (NA), that is consistof three divisions and twolaboratories (Fig. 2). Especially
two sections at NA, Physics andChemical sciences (NAPC) andHuman health (NAHU) assume important roles for BNCT.
A key objective of NAHU is to support member state’s fight against cancer,
cardiovascular diseases and malnutrition and other diseases using nuclear and nuclearrelated techniques, this is accomplished thorough support of cancer radiotherapy
treatment and diagnostic imaging projects as well as support of nutrition centers andhuman resource development. NAPC assists member states with capacity-building,research and development in the nuclear sciences and supports them in using nuclear
methods for a variety of practical industrial applications.
In 1999, Technical
Meetingon
Neutron Capture
Therapy was held
and
IAEATECDOC-1223“Current status of neutron capture therapy” was published [3]. With the development ofaccelerator based BNCT from reactor based BNCT, the side event of 60th General
Conference was held as “Recent Advances in Boron Neutron Capture Therapy Using
Research Reactors and Accelerators” in 2016 (Table 1). After Najat Mokhtar was
appointed Deputy Director General and head of NA on January 2019, the collaboration
framework between NAPC and NAHU have set up. On October 2019, Consultancy
Meeting on BNCT ‘current status and new developments’ was held at IAEA by NAHU
and NAPC and the technical meeting on BNCT will be planned in 2020.
I would like to thank Dr. Kato for this opportunity.
Ref.
[1] https://www.iaea.org[2] http://www.crms-jpn.org/doc/IAEA-WHO1959.pdf
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NCT letter Issue 6 June 2019[3] https://www.iaea.org/publications/6168/current-status-of-neutroncapture-therapy

Report on the 15th Japanese Congress on Neutron
Capture Therapy
President
Masayori Ishikawa
Professor, Graduate School of Health Sciences, Hokkaido University“The 15th Congress on Neutron Capture Therapy” was held at the Hokkaido
University Conference Hall on September 1st (Sat) and 2nd (Sun) 2019. The 6th BNCT
Workshop (hosted by the Human Resource Development Committee of the JapaneseSociety of Neutron Capture Therapy and supported by this Congress) was held on the day
before the Congress of August 31st.
It was very fortunate to be welcome participants in the refreshing climate unique to
Hokkaido. In addition, a typhoon hit directly on September 4 immediately after the
congress, and an earthquake of seismic intensity 7 occurred in Hokkaido before dawn on
the 5th, and the entire Hokkaido was blacked out by the earthquake. Since the days ofnatural disasters continued, it would be impossible to held the congress if it had beenscheduled one week after.
At the congress, 163 participants (79 regular members, 58 non-members, 26 students)
joined the congress to present latest research results and make hot discussions in the fields
of clinical medicine, pharmacy & chemistry, biology, and physics. I am full of gratitude
for all the participants with their passion to
BNCT.
Boron Neutron Capture Therapy (BNCT)
is now on transition stage from irradiation
based on research reactor to irradiation using
accelerator-based neutron source and that
may enable much more facilities to provide
BNCT. The quality of the therapy has been
secured by choosing the best therapy throughtrial and error for each case, however, toGeneral presentation and poster session
enable equivalent therapy to be provided by
the facilities which are assumed to increase in the future, it is essential to share theconsensus on the base technology and to establish the process of quality
management/quality assurance of BNCT. For that purpose, the 15th Congress was held
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NCT letter Issue 6 June 2019with the theme “Towards Establishment of Base Technologies to Improve Therapy
Quality”. BNCT is generally categorized into three fields; medicine & biology, physics& engineering and chemistry & pharmacology. The established technologies andtechnologies that still need to be discussed are mixed in each field. In the field of medicine& biology, careful discussion is necessary on prescribed dose and normal tissue tolerance
dose in association with expanding the applicable diseases and devising the irradiation
methods. In the field of physics & engineering, the appearance of irradiation facilities
using accelerator-based neutron source raises the need to establish technologies formeasuring and controlling precise neutron exposure. In the field of chemistry &pharmacology, establishment of methods for quantitative assessment of drug
accumulation in tumors are the critical issue, as well as the new drug development.
The numbers of the presentations were 66 in total, consisting of 1 educational lecture,
1 luncheon seminar lecture, 6 symposium lectures, 40 general presentations and 18 poster
sessions. Questions and answers were vigorously exchanged at the end of eachpresentation, the discussions were based on a view point of clinical necessity of each field.
Meanwhile, those discussions were in line with each presentation which was among manyother themes requiring a lot further discussions.
The educational lecture with the theme of “Development of synthetic diamondradiation detectors as well as semiconductor device and GPS scintillator” was deliveredby the invited speaker of associate professor Junichi Kaneko (Graduate School/Facultyof Engineering of Hokkaido University), who has a lot of experience in developing
neuron detecting element.
“Challenges for the establishment of base technologies” was the theme of thesymposium and six speakers offered presentations of 1: Current status and challenges of
BNCT as a part of multidisciplinary approach, 2: Current status and challenges withregard to development of next generation boron agents for BNCT, 3: Base technologies
of medical physics and engineering necessary to predict biological effect, 4: Current
status and challenges of treatment planning software for BNCT, 5: Establishment of
irradiation facilities/ irradiation technique for diversification of BNCT, and 6: Quality
control/quality assurance of BNCT as radiotherapy. Throughout the session, current
conditions and challenges in the field of clinical medicine, drug development and physicalengineering were reported while guidelines for establishment of the base technology were
presented.
More than 100 participants attended congress dinner held at the Faculty House
Trillium “Restaurant Elm” located in Hokkaido University. Attendees of the dinner party

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NCT letter Issue 6 June 2019were entertained by the string quartet of
Hokkaido University Symphony Orchestra that
performed works by Dvorak and Mozart.
Finally, I would like to express myString quartet entertained attendees of
the congress dinner.

appreciation to Prof. Hiroyuki Nakamura, thePresident of the Japanese Society of Neutron
Capture Therapy, Prof. Takai Yoshihiro, thechairman of the previous congress, Prof.
Hironobu Yanagie, the chairman of the 13th
congress and the members of the Society for

their various fruitful advice, and to the staff ofthe management secretariat for their valuable
efforts made for the management and practicalbusiness for this congress, secretariat of Convention Linkage, Inc., and students of mylaboratory. Let me also express sincere appreciation toward 17 companies which
supported the management of this congress in the form of placement of advertisements,
setting up of booths and sponsorship.
For further details of this congress, please refer to the “Information on Nuclear
Technology in Medicine” Vol. 19 issued by the Association for Nuclear Technology in
Medicine.

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NCT letter Issue 6 June 2019

Participation to ICNCT18 (Taipei)
Associate professor
Hiroaki Kumada
University of Tsukuba Faculty of Medicine, Proton
Medical Research Center
The 18th International Congress on Neutron Capture Therapy (ICNCT18) was held in
Taipei from October to November 2, 2018. Since I participated in this international
academic convention, I will introduce my impressions from my perspective of thisconvention.
First, this international convention has been held in rotation between Japan, Europe andAmerica (including South America.), this time it was Japan’s turn but, for the first time
was held in a place other than Japan (In principal, the rotation rules for this venue havedisappeared.) Taiwan, with its Tsinghua University Nuclear reactor: currently
conducting clinical research using THOR, is one of the world’s highest BNCT activity
regions. It can be said that it was natural for this convention to be held in Taiwan. Also,
based on recent Asian BNCT activities, places to hold this convention will continue tobe selected from “Asia” instead of “Japan”. Starting with Convention President
Professor Fong-In Chou (picture 1), the support and program structure of the society
secretariat, this was a convention where we could feel the enthusiasm “let’s make thisconvention a success!” Personally, through participating in this convention I was able toenjoy this place called Taiwan, its people and atmosphere.
Looking at the convention’s program, first off, “Educational sessions “and multiple“Invitation sessions” were quite distinctive. At previous conventions, on the first day fromthe “Welcome Reception” it was fine to simply participate at our ease, but at thisconvention before the “Welcome Reception” a 150 minute “Training Course” was set up
with educational lectures by 4 instructors of different fields. I was also impressed by thefact that many of the participants in this session were not only students and young
researchers but also experienced researchers. Regardless, many participated from start tofinish, listening enthusiastically. This “Training Course” session was a good project that
I hope will be continued in the next conventions onward.
In addition, the “Invited Lecture” sessions, which were held four times from the second
day with each session having lectures given by 3 to 5 researchers from different fields,
was an interesting program structure.

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NCT letter Issue 6 June 2019

In the general program configuration, Plenary
Lecture session：5, Parallel Session：6,
Poster Session：2, as well as Luncheon Seminar：
2 were set.
My impression was that the total number ofpresentations was larger than at the previous 17th
convention (University of Missouri, US) and it
seemed as though the convention secretariat had
set more oral presentations （ At the lastconvention, Plenary Session：9, Parallel Session：

写真１ Opening Ceremonyで開会をProfessor Fong-In Chou declared the start
宣言する大会長のFong-In Chou先生of the congress at the opening ceremony

4, Poster Session：3）.
This is probably because many researchers from Japan were able to participate because
the venue was held in Taipei, and many new researchers from China and South Korea
also participated. Also, it is probably because of the high level of interest in BNCT in
Taiwan. Looking at the number of presentations in each field, as could be expected, I feltthat many presentations were about physical engineering and were very active. This is not
only because I mainly participated in physical engineering sessions, but also looking backat the program for the entire convention many such programs were set. The number ofsessions for both Plenary and Parallel was “Clinical”: 3, “Chemistry & Pharmacology”:4,“Boron Detection & Imaging”: 3, “Radiobiology “:3, “other”: 2, “Physical Engineering”
was 8 sessions. Although this trend has been seen for quite a while, this is probably
because research and development of the “accelerator-based neutron source device” hasbeen actively carried out worldwide, and new research institutes and companies havestarted to enter this field of research. I especially feel that, as mentioned above, research
institutes and companies in new regions such as China and South Korea have entered the
BNCT field. Quickly counting, there were 16 presentations from China and South Korea.
It was also introduced that 2 venture companies in the US, where BNCT activity has been
limited so far, have entered the development of commercial accelerator-based treatment
devices, and will also be implemented in Finland, China and Italy. Japan has been theworld leader in this field so far, but it has become so that we have no time to waste. On
the other hand, “clinical” related presentations are undeniably decreasing since there are20

NCT letter Issue 6 June 2019

only 4 nuclear reactor facilities in the world where research can be conducted. However,this tendency is likely to be realized in the near future when accelerator-based treatment
devices are put into practical use, if treatment with the devices start, the number ofpresentations will increase, we can expect this to become the main session of theconventions again. At the earliest, at the next convention (Grenada) or perhaps the one
after (Poland), there may be presentations related to treatment with accelerator-based
treatment devices and clinical research. Personally, including hopeful observations, I
hope the first presentation will be by a Japanese group.
Finally, I will introduce the changes in the structure of the International Society on
Neutron Capture Therapy (ISNCT), which is the basis of this academic conference. Until
now, the president of the ISNCT was also the chairman of the next academic convention,
which changed every two years. However, in order to operate this international society
stably and continuously, and to develop BNCT research internationally, starting fromthis convention, as with regular conferences, apart from the convention president, a“President”, “Vice President” and “Secretary” were established, and Professor Porras(Spain), Professor Matsumura (Japan) and Professor Bortolussi (Italy) were appointed
respectively. With the evolution of this society and the BNCT “heat” felt in Taiwan, I
hope that BNCT research will accelerate further and that it will be established anddeveloped worldwide as an effective cancer treatment.

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NCT letter Issue 6 June 2019

Report of BNCT session at AACR (American
Association of Cancer Research), 2019
Akira Matsumura
Professor, Department of Neurosurgery, University ofTsukuba Hospital

From 29th March to 3rd April, 2019, a major symposium of BNCT was held at AACR,
2019 (Georgia World Congress Center,
Atlanta, Georgia, USA).
The BNCT session was held on 31st Marchfrom 13 to 14:45 in a relatively big room. At
the same time, about 20 parallel sessions weregoing on so that there were not so strikingly
many participants, but there were active
questions and discussions from the audience.
At AACR (from left; Matsumura,
Koivunoro, Kankaanranta, Barth )The chairman of the BNCT session was Dr. Leena Kankaanranta from Helsinki
University. The first speaker was Dr. Rolf
Barth from Ohio State University presenting the results of their own experimental using
F98 brain tumor model and the reviewed the clinical results of head and neck cancers andmelanomas. He also mentioned the usefulness of BNCT in combination withchemotherapy and immunotherapy as a part of multidisciplinary treatment, He also
referred the paper by Prof. Hiratsuka in urogenital melanoma and stressed theimportance of preserving normal structure of sensitive part of the body. The second
speaker was Dr. Hanna Koivunoro from Helsinki University and told about the
principles and issues and medical physics issue of BNCT. She also introduced the BNCT
accelerator system, patient setting system and treatment planning system installed in
Helsinki University. As unpublished data, she presented that the clinical results aredifferent among patient received below and above 18Gy-Eq. Next speaker was Dr. Leena
Kankaanranta from the same institution presenting the clinical results of BNCT treatment
in head and neck cancer and stressed that BNCT is extremely effective in recurrent cases
22

NCT letter Issue 6 June 2019

compared to other radiation therapy. Finally, Dr. Akira Matsumura from University ofTsukuba presented the principles of BNCT, characteristic of BSH and BPA, developmentof 18F-BPA PET and its benefit for selection of indicated cases for BNCT and boron dose
estimation using 18F-BPA PET images. The development of Epithermal neutron beamwith usage of treatment planning system was also introduced. The Japanese status ofaccelerator based BNCT was also demonstrated.
In general discussions, many questions about clinical trial were raised reflecting theinterest towards BNCT as clinically available treatment modality. Especially, newboronated drugs were also of big interest of the audience because after accelerator has
been established, new boronated drugs would become big research target in thepharmaceutical field.

Presenting BNCT at a big major
conference like AACR was a big
opportunity for BNCT and spreading theinterest of BNCT to researchers who havenot been familiar to BNCT would be also
an important step to expand the BNCT in
the future.

The room for BNCT session（A302）with a capacity for over 100 participants

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NCT letter Issue 6 June 2019

The 10th Young BNCT Meeting 2019
Ignacio Porras
President of ISNCT
Departamento de Física Atómica, Moleculary Nuclear Facultad de Ciencias
Universidad de Granada

The biannual meeting of the young researchers working in BNCT is an event that takes
place since many years and it is consolidating as a fruitful moment to exchange ideas,
train the newcomers in this research field and establish close networks across Countries.
Young researchers can present their results, chair sessions, and give rise to discussion ina friendly and less official atmosphere. As we are all fostering BNCT as a future therapy
to fight cancer, it is important to motivate and generate enthusiasm in the new generationsof BNCT scientist. Welcome to the next edition of YBNCT in Finland!

Hanna Koivunoro
Medical Physicist at Neutron Therapeutics Inc
FinlandDear Colleagues and Friends,
The 10th Young Member’s Boron Neutron Capture Therapy (YBNCT) meeting will beheld in Helsinki Finland, September 26-29, 2019. This year is remarkable in the historyof BNCT. Finally, clinical accelerator based neutron sources are becoming a reality for
BNCT. This year, the BNCT society is eagerly awaiting the results of the first clinical
trials of head and neck, and brain cancer performed at the accelerator based BNCT
facilities in Kyoto Research Reactor Institute and Southern Tohoku General Hospital,
Japan. University of Tsukuba and Tokyo National Cancer Center are about to start theclinical trials using two different types of accelerator based neutron sources. At the sametime, after some quiet years for clinical BNCT in Europe, the first Western accelerator
based BNCT facility is under commissioning at Helsinki University Hospital in Finland.

24

NCT letter Issue 6 June 2019

The year 2019 is the year of the Pig, the last of the zodiac animals. According to a story,
the Pig was late because he overslept. Another story says that a wolf destroyed his house.
He had to rebuild his home before he could set off. When he arrived, he was the last one
and could only take twelfth place. The Pigs are considered successful later in life, andassociated with the wealth and fortune.
BNCT and the Pig share their spirit; ever since the emergent idea of G. L. Locher in 1936
and the first clinical trials by W. H. Sweet at Massachusetts General Hospital in 1951,
BNCT has been slowly, but patiently built to become a promising radiotherapy modality.
I trust BNCT will also be successful soon, later in its life. Thanks to the bright andenthusiastic BNCT researchers worldwide with the common aim, to make BNCT one
additional therapy modality for cancer patients in need.
This year, we also celebrate the 10th anniversary of the biennial YBNCT meetings. The
YBNCT meetings have been a great success ever since the first meeting in Petten,
Netherlands, in 1999.
On behalf of the organizing committee, I proudly invite you to Helsinki during the foliage
season to hear the latest BNCT news, listen to talks of BNCT researchers, and to enjoy
the discussions with our cheerful young at heart society members.

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NCT letter Issue 6 June 2019

Notice on the 16th Congress on Neutron Capture
Therapy
President Minoru Suzuki
Professor, Institute for Integrated Radiation and
Nuclear Science, Kyoto University
I am Minoru Suzuki from the Institute for Integrated Radiation and Nuclear Science,
Kyoto University and I was appointed Chairman of the 16th Congress on Neutron Capture
Therapy.
The Congress will be held on September 7th (Sat) and September 8th (Sun) 2019 at
Uji Obaku Plaza in Uji Campus, Kyoto University, located in Uji City, Kyoto Prefecture.
For details, please refer to:（http://jsnct16.umin.jp）and we would appreciate it if manyof those concerned could participate. The theme of the 16th Congress is “Thinking about
the Diversity in Neutron Capture Radiation (NCR) Research.” The aim of the theme isshown on the Congress website in the message from myself as the Congress Chairman.
Hereby I would like to add a little bit more about the aim of the Congress.
The Japanese Society of Neutron Capture Therapy is an academic society which
consists of researchers from diverse areas such as medicine, engineering, pharmacology,
etc. “Neutron capture therapy” is a name of the treatment method and researchers withdiverse backgrounds are working on their research with their own approach to advancethe medical treatment called neutron capture therapy. As neutron irradiation is necessary
for such research, many members of our society are jointly using the Kyoto University
Research Reactor (KUR) at the Institute for Integrated Radiation and Nuclear Science,
Kyoto University (hereinafter called ‘the Institute’) every year. About one third of theresearch topics adopted by the Institute in the year 2019 is related to neutron capture
therapy.
As I mentioned on the Congress website, 6 years later KUR is scheduled to be shut
down and decommissioned. Although utmost effort will be made to enable the provisionof neutron irradiation field by accelerators after the KUR shut-down, I expect it would be
difficult to have the same level of availability as the neutron irradiation field provided by
KUR. In order to arrange a new neutron irradiation field at the Institute as well as
arranging the neutron irradiation fields for the basic research in several locations in Japan,
it is important to expand the range of neutron research. To that end, in this Congress, wehope that not only the above-mentioned research goal will contribute to the neutron
26

NCT letter Issue 6 June 2019

capture therapy which is a radiation therapy for cancer patients but also the researchachievements or preliminary research achievements will be presented to give someinspiration to the research themes contributing to the entirely different disciplines.
With such expectation, the theme of this Congress was set forth as “Thinking about theDiversity in Neutron Capture Radiation (NCR) Research.” Boron Neutron Capture
Therapy (BNCT) can play a role as a very unique radiation therapy, which destroys cancer
cells selectively by NCR. If boron compound could be delivered to the arbitrary cell
fraction in the body, such cell fraction could be exclusively destroyed. Basic research on
selective irradiation of vascular endothelial cell and selective irradiation of macrophageis already reported as a B(NCR) research paper. Perhaps Auger electron by GdNCR could
also produce some unique research achievements? As you can see, the research tool NCR
could be applied to research in the disciplines such as radiobiology, botany, pharmacology,
etc., which are unthinkable for a medical doctor like myself.
In this Congress, I do not expect that there will be so many research presentations
which will take into account the diversity of NCR research. However, I hope that as many
young researchers as possible will engage in unique research using neutron by applying
NCR as one of their research tools, and in the future such research will involve otherresearchers around them. As a professor at the Institute, for many years I have been
supporting the research of many researchers who jointly used KUR. From this experience,
I strongly feel the significance of having to arrange the irradiation field for neutron
capture therapy research.
Every year KUR is jointly used by many of those who are involved in neutron capture
therapy. Many researchers including graduate students and young assistant professors areusing KUR. When I see young researchers presenting their papers on their researchachievements made by jointly using KUR, I feel happy as if they are my own researchachievements. I truly hope that more and more young researchers will engage in basic
research on neutron capture therapy or NCR basic research.
Some of you may find it difficult to get a sense of the theme of this Congress,“Thinking about the Diversity in Neutron Capture Radiation (NCR) Research.” I would
be glad if you could understand from my message here that the theme implies ouracademic society’s determination that we are seriously going to work on expanding therange of NCR research towards the arrangement of the irradiation field for neutron
capture radiation therapy research in the future. Finally, we hope that many of you will
participate and register your presentation subject so that this academic congress will be a“hot” event, which is even hotter than the temperature in Kyoto on September 7 th and 8th
when the lingering summer heat is expected.
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NCT letter Issue 6 June 2019

We are happy to announce to you the definitive dates for next
year ICNCT meeting.

Javier Praena
Congress Chair of ICNCT-19

Ignacio Porras
President of ISNCT28

NCT letter Issue 6 June 2019

The Best Presentation Award of the 15th Annual Meeting of Japan Society
for Neutron Capture Therapy
Development of the cylindrical neutron spectrometer for
accelerator-based BNCT irradiation field.
Kentaro Baba
Graduate School of Biomedical Science and Engineering,
Hokkaido University
In recent year, accelerator-based neutron sources for BNCT have been developed. For
estimation of the neutron energy spectrum, the Bonner sphere spectrometer combining
neutron moderator with different sizes and neutron detector has been widely used.
However, time and effort are required because it is necessary to change the moderator
and make many measurements. Therefore, we focused on the Scintillator with OpticalFiber (SOF) detector, an ultra-small real-time thermal neutron detector. Most of thematerials that make up the SOF detector are made of plastic, the effect of the SOF
detectors on the neutron transport of the moderator is not greater compared to the casewhere the insertion holes are filled with moderator materials. Therefore, we consideredthat there is a possibility that neutron energy fluence can be estimated by one
measurement by incorporating a plurality of SOF detectors in a row from the moderator
surface and changing the depth. This is because even when the SOF detector isincorporated inside the moderator, it can be treated as a uniform moderator.
The cylindrical spectrometer was composed by combining an acrylic cylinder (material:
PMMA, density: 1.18 g/cm3, diameter: 100 mm, length: 300 mm) and twenty-one SOF
detectors. The SOF detector was placed from the position of 1.5 mm from the cylindricalsurface along the central axis of the cylindrical moderator to the range of 201.5 mm fromthe cylindrical surface in 10 mm steps. The response function was calculated considering
the angular distribution.
Measurements were performed using neutron beams in the Neutron Accelerator System
for Biological Effect Experiments (NASBEE) at the National Institute of Radiological
Sciences (NIRS), and neutron energy spectrum was evaluated by the unfolding method.
Compared with the simulation result by the particle transportation Monte Carlocalculation code Geant4 ver.10.03.p03, the relative error of fast neutron fluence agreed
with less than 1%, and the relative error of thermal and epithermal neutron fluence agreed
with less than 10%. The proposed cylindrical neutron spectrometer was able to easily
29

NCT letter Issue 6 June 2019obtain many measurements of different energy response characteristics by changing thedepth at which the SOF detector was placed. Moreover, since there is a possibility thatthe neutron energy spectrum can be estimated by a single measurement, the system
combining the SOF detector and the cylindrical moderator is considered to be a highly
practical neutron spectrometer.
Finally, I would like to thank Prof. Masayori Ishikawa, the president of the 15th Neutron
Capture Therapy Academic Conference, who selected this presentation as the best
presentation award. I am grateful to Prof. Itsuro Kato for giving me the opportunity towrite with the NCT Letter.
【reference】
1．M. Ishikawa, et al., Development of a wide-range paired scintillator with optical fiber
neutron monitor for BNCT irradiation field study. Nucl. Instrum. Meth. A 551 (2005) 448457.

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NCT letter Issue 6 June 2019

The Best Presentation Award of the 15th Annual Meeting of Japan Society
for Neutron Capture Therapy
Enhancing therapeutic potential ofboronophenylalanine by controlling its metabolism
using biocompatible polymers
Takahiro Nomoto1, Yukiya Inoue1, Ying Yao1, Minoru
Suzuki2, Kaito Kanamori1, Hiroyasu Takemoto1, Makoto
Matsui1, Keishiro Tomoda1, Nobuhiro Nishiyama1
Laboratory for Chemistry and Life Science, Institute of
Innovative Research, Tokyo Institute of Technology,
2
Research Reactor Institute, Kyoto University
1

Boronophenylalanine (BPA) is taken up into a cell via the amino acid transporter LAT1,
which is overexpressed in many tumor cells, and thus can selectively accumulate intumors. In addition, a BPA derivative (18F-BPA) modified with fluorine (18F) permits
companion diagnosis by positron emission tomography (PET), and BPA is an extremely
useful drug in clinical practice. However, intravenously injected BPA does not always
show long tumor retention. To maintain the intratumoral boron concentration necessary
for obtaining a therapeutic effect, BPA needs to be additionally administered during
thermal neutron irradiation. In clinical situations, BPA is additionally administered byinfusion. However, this technique may complicate the procedures, resulting in increaseof the treatment time spent on a patient. This raises the concern that usage time of neutron
source cannot be efficiently utilized.
One possible explanation for the short retention time of BPA in tumors is theexchange transport mechanism of LAT1. When LAT1 takes an extracellular substratesuch as phenylalanine into the cell, it exports the intracellular substrate such as glutamine.
The reverse phenomenon may also occur. For example, when the extracellular BPA
concentration decreases, extracellular amino acids are expected to be exchanged withintracellular BPA. A previous study about metabolic pathways of BPA indeed reported
that intracellular boron concentration could be maintained at a high level in the absenceof extracellular LAT1 substrates [Radiat. Res. 153, 173-180 (2000)].
Hence, to avoid the unfavorable efflux of intracellular BPA, we conjugatedmultiple BPA molecules to a biocompatible polymer, polyvinyl alcohol (PVA) through31

NCT letter Issue 6 June 2019boronate esters. In this structure, the boronic acid moiety of BPA contributes to the
conjugation, preserving the amino acid structure that has affinity for LAT1; thus, the PVABPA complex is expected to be recognized by LAT1 and internalized through endocytosis.
Confocal laser scanning microscopy indeed illustrated that PVA-BPA was localized in
endo/lysosomes whereas the fructose-BPA complex was transferred to the cytoplasm. In
cellular uptake evaluation, a system L inhibitor significantly reduced the uptake of PVABPA. This evaluation also indicated that PVA-BPA retained in the cell for a longer timecompared to fructose-BPA. These results suggest that PVA-BPA was taken up into cells
through LAT1-mediated endocytosis, thereby suppressing the unfavorable efflux of BPA.
To investigate whether similar effects can be obtained in in vivo, we evaluatedthe accumulation of fructose-BPA and PVA-BPA in subcutaneous tumor models.
Fructose-BPA showed extremely high tumor accumulation 1 h after intravenous injection,
but significantly decreased the intratumoral boron concentration after 3 and 6 h. On theother hand, PVA-BPA could maintain the high concentration even after 6 h, reaching thetumor accumulation level equivalent to or higher than that of fructose-BPA 1 h afteradministration. In general, macromolecular drugs remain in the blood or accumulate in
the liver, but the molecular weight of PVA used in this study was about 10,000, permitting
efficient renal excretion and eventual quick clearance from the blood and normal tissues.
To examine the effect of the intratumoral retention of BPA on the antitumor effect, BNCT
was performed on subcutaneous tumors at the Kyoto University Research Reactor. PVABPA exhibited significantly higher antitumor activity than fructose-BPA. These results
strongly indicate that PVA has the potential as an additive for improving the therapeuticpotential of BPA. In this study, we used PVA as the platform because of its excellent safety.
Since the dose of BPA is 500 mg/kg, the amount of the administered polymer is inevitably
high. In this regard, PVA has an extremely simple structure and has been studied as a
biocompatible material for many years; PVA has been used as a pharmaceutical additive.
Furthermore, because PVA-BPA can be easily prepared by mixing PVA and BPA in water,
18
F-BPA with a short half-life is also expected to be easily incorporated into this system.
To translate this research to practical application, we are currently optimizing the structure
for a nonclinical study.
Finally, I would like thank Prof. Masayori Ishikawa, Prof. Hiroyuki Nakamura,and Dr. Itsuro Kato for giving me the opportunity to introduce this study. I would also
like to express my deep appreciation to Dr. Yoshinori Sakurai, Hiroki Tanaka, and Takushi
Takata for their kind support in neutron irradiation.

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NCT letter Issue 6 June 2019

The Best Presentation Award of the 15 th Annual Meeting of Japan
Society for Neutron Capture Therapy
Development of neutron capture therapy using boronbinding adenovirus vector
Sayuru Tsuyuguchi, MD
Department of Neurosurgery, Graduated School of
Biomedical and Health Sciences, Hiroshima University

The problem with boron neutron capture therapy (BNCT) for malignant glioma is their
low permeability through the blood-brain barrier (BBB). Therefore, we have beenaddressing the research on development of novel boron drug delivery system (DDS)
through the infection of the adenovirus vector conjugated with boron compound.
Human malignant glioma cell line, (U251MG) and replication-defective adenoviral
vector expressing LacZ gene were used in this study. Evaluation of adenovirus gene
expression was examined by β-gal staining. The boron compounds bound on the
adenovirus surface were BODIPY, a fluorescent boron compound (CellTracker ™ GreenBODIPY®), and a colloidal gold compound (NANOGOLD), which binds to the SHgroup on the virus surface via a maleimide group. Inductively coupled plasma atomic
emission spectroscopy (ICP-AES) was used for intra-cellular boron determination. An
electron microscope was used for determination the adenovirus vectors bound the
NANOGOLD.
U251MG cells infected with BODIPY-conjugated adenovirus vector were yielded
fluorescence, while the intracellular boron concentration was extremely small, andinsufficient for BNCT. An electron microscope was shown that adenovirus vectors
conjugated with NANOGOLD were detected in both cytoplasm and nucleus of the
U251MG cells after infection of NANOGOLD-conjugated adenovirus vector. In addition,
the expression of the LacZ gene was detected by β-Gal staining in the U251MG cells after
infection of NANOGOLD-conjugated adenovirus vector.
The transfection efficiency could be maintained even when the NANOGOLD compound
was bound on the adenovirus surface via a maleimide group in our study condition. In
addition, adenoviruses are also accumulated in the nucleus, and we believe that BNCT
can be expected to have a higher cell killing effect. Further studies with neutron
irradiation has now been considered in order to apply boron compound-modified
adenovirus for novel BNCT treatment as verifying the therapeutic effect and elucidating
DDS.
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NCT letter Issue 6 June 2019

As the next step, we are accumulating data on neutron irradiation experiments for boron
compound-modified adenovirus, and we aim to apply it to future BNCT treatment byverifying the therapeutic effect and elucidating DDS.

34

NCT letter Issue 6 June 2019

In receiving the Special Award, Global Outstanding
Achievement Award (18th ICNCT)
Koji Ono
Director
Kansai BNCT Medical Center, Osaka Medical College
It was my honor to receive the above award at the 18th International Congress on Neutron
Capture Therapy held in Taipei from October 28th to November 2nd, 2018. The Congress
bestows Hatanaka Award granted to researchers for their competent contributions andFairchild Award granted to young researchers. Hatanaka Award is granted forcontributions to research activities in individual area such as clinically specific cancer,
chemistry, physics or biology, whereas, the Global Outstanding Achievement Award, as
the name shows, has a different focus. This award honors comprehensive achievements
in studies of BNCT. I assume that the staff concerned in the Congress in Taipei dared togive me the award to express their gratitude for my support for the Taiwan BNCT. I would
first like to mention about this point. I first met Taiwan’s BNCT researchers in October
2008 when the JASTRO Congress was held in Sapporo, through the mediation of Prof.
Yasushi Nagata of the Department of Radiation Oncology, Hiroshima University (he is 9
years younger than me at Kyoto University). Another member of JASTRO, Prof. Junichi
Hiratsuka of Kawasaki Medical School also joined the meeting. To my surprise, researchon BNCT and preparation for starting clinical studies had already been in progressconsiderably in Taiwan. I was ashamed of myself for not knowing the fact. We thencooperated in the 1st case using the Tsing Hua Open Pool Reactor (THOR) at National
Tsing Hua University and the 2nd case of BNCT for recurrent head cancer. I taught the
Taiwanese researchers in detail about the two-step rate administration method of BPA,
which was my idea, together with its background perspective, and also about the dose
assessment method, perspectives on tumor dose and normal tissue dose, and CBE factor.
The radiation facility of THOR, having been built after KUR and JRR4, has an excellent
design presenting high neutron flux as well as optimum beam port height and collimator.
It goes without saying that the success in the first 2 cases led to the continuing
implementation of clinical studies. I also assisted in accepting Dr. Yi-Wei Chen and otherdoctors and medical physicists to Kyoto University Research Reactor Institute for training,and held some research meetings with the Taiwan group. For these purposes, my visit to
Taiwan exceeded 10 times and, beyond this award, I had the honor of having my namementioned twice with deep appreciation by Mr. Lee Teng-hui, the former President of35

NCT letter Issue 6 June 2019

Taiwan, when he made a congratulatory speech at the international academic conference.
Taiwan has become the second advanced country in the field of BNCT research after
Japan in Asia. I look forward to the further development in Taiwan and would like to offer
any support I can do.
BNCT is a therapy which is much more interdisciplinary compared with other radiation
therapies. It relates with various areas of clinical radiology such as radiation oncology,
nuclear medicine, and diagnostic radiology, as well as other related clinical areas andother basic areas such as physics, chemistry, pharmaceutical sciences and biology.
Therefore, a headquarter to coordinate studies in these areas and successfully lead thewhole research on BNCT is essential. A group with functions like the military staff
headquarters is required. In 1991, I was transferred from Faculty of Medicine, Kyoto
University to Kyoto University Research Reactor Institute (KURRI) in Kumatori. It was
fortunate for me that the institute had Radiation Oncology and Medical Physics divisions
that specify in BNCT research, and the cooperative division of Radiation Biology, which
is why the KURRI has led BNCT research not only in Japan but also in the world fromthe 90s onward. Considering the role that KURRI should play, my group gave priority tobasic research and technology development. Starting the research with Prof. Masunagaon the elucidation of the difference in radiation effects between BPS and BSH andworking out how to overcome their respective weaknesses caused by the difference. Other
researches include two-step rate administration method of BPA, BPA administration via
intra-arterial tube, use of epi-thermal neutrons in place of thermal neutron, complete presetting of the patient’s position and posture at the preparation room and automatingtransport to the irradiation room, joint basic research with Prof. Suzuki on application of
BNCT to liver cancer, with medical physics group on central shield of irradiation field
for improving depth distribution of neutrons, non-invasive injection of air into the deadspace left after tumor resection, development of γ-telescope for liver cancer BNCT, joint
research with Prof. Kinashi on the influence of whole-body exposure. I also led clinicalstudies, however, I left the initiated clinical studies to the doctors of the related
departments as far as possible since the KURRI has no clinical hospital. I believe thisexpanded the network among researchers and cultivated their abilities. Based on the
results of these studies, we were able to achieve the goal of developing the world's first
BNCT dedicated neutron irradiation system in collaboration with Prof. Maruhashi's
medical physics group and Sumitomo Heavy Industries, Ltd.
Irradiation in clinical trials has already been completed. I hope we can obtain the approvalof BNCT from the Ministry of Health, Labour & Welfare in 2020 and start clinical BNCT
using cyclotron neutrons.
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NCT letter Issue 6 June 2019

More than 30 years have passed since I started studying BNCT, however, there are many
points yet to be solved from the viewpoint of radiation oncology. I myself want tocontinue to tackle unsolved problems.

37

NCT letter Issue 6 June 2019

Hatanaka Award (18th ICNCT)“On receiving the Hatanaka Award”
Mitsunori Kirihata
Professor of the Laboratory for Medicinal Chemistry
for Boron Drug, Research Center for BNCT,
Organization for Research Promotion, Osaka Prefecture University
Preface
I had an honor to receive Hatanaka Award at the 18th ICNCT held in Taipei on October
29th, 2018. My earning such distinction is fully attributed to the staff of the former
Chemistry of Biological Control Laboratory and Laboratory for Medicinal Chemistry for
Boron Drug, graduates and research students, and also to those who gave me direct andindirect assistance and cooperation through joint researches and obtaining competitive
research funding. I would once again like to express my gratitude to everyone concerned.
① “Memoir”
I remember that I became involved with BNCT in 1987 or 88, a few years after I returnedback from studying abroad. In those days, we considered natural non-protein amino acids(unusual amino acids) as the seeds for medicines and agricultural chemicals and usedsome of unusual amino acids having significant biological activity, includingorganophosphorus amino acid, as lead compounds to develop asymmetric synthesis
method of such amino acids and to clarify the mechanism of the onset of activity andstructure-activity correlation, employing techniques of organic chemistry. At that time,
Dr. Yoshinori Kitaoka of KUR introduced us the cancer therapy using BNCT and thesynthesis of D,L-BPA developed by Snyder. This became the springboard for me to get
into this field. Since then, I added boron agent research as one of the themes of thegraduation/master’s theses, and in the 1990s, I conducted high-volume synthesis of D,LBPA and its derivative with ethyl isocyanoacetate as the synthesizing element,
asymmetric synthesis of L-BPA with bis-lactim ether as chiral auxiliary molecule,synthesis and biological evaluation of BPA derivative containing o-carborane, in order toclarify activity correlation between indispensable structure of BPA and tumor
accumulation.
The 10BPA BNCT initiated by Prof. Mishima in 1987 served as the basis for today’s
progress in BNCT. In those days, L-10BPA imported from the United States was expensive
and had problems such as long delivery time and unstable supply. Clinical studies of10

BPA BNCT showed progress in the 1990s and the demand for 10BPA BNCT increased
38

NCT letter Issue 6 June 2019accordingly, therefore, domestic production became necessary for stable supply in the late
1990s. I received requests for domestic production of L-10BPA from many doctors andprofessors and then I used to respond saying that domestic supply of 10B-boron (ingredientof L-10BPA) was the bottleneck.
The turning point was in 1999 when we came to know that a manufacturing plant ofhighly-condensed 10B-boron (Stella Chemifa Corporation) was located in the neighboring
Izumiotsu City, just 15km away from our campus. Until then, I had assumed that allsynthesis materials of 10B-boron had to depend on import from the US, therefore, knowing
this was like a thunderclap to me. I was filled with surprise and gladness, and felt
disappointed with myself at the same time for not knowing the local circumstances. Later,
I visited the plant to confirm the manufacturing method of 10B-boron, its purity ofcondensation, quality and annual production. The condensed 10B-boron manufactured in
the plant was useful not only for L-10BPA but also as a starting ingredient widely
applicable to 10B-boron agents for BNCT, and thus was suitable for the domestic
production of L-10BPA, solving the pending issues of ingredients.
In 2000, the demand for domestic production of L-10BPA and 10BSH increased further
according to the increase in the number of cases. We considered that the overriding
priority should be given to strong industry-academia-government collaboration toestablish manufacturing methods of high-quality L-10BPA and 10BSH using domestic
technology and domestically-produced 10B-boron, with the purpose of developing new
drugs. Upon this view, a research consortium in which universities, industries andresearch facilities participate was constructed in 2002. Moreover, a laboratory base wasorganized in 2005 in the Innovation Plaza Osaka (later closed down) of the Japan Scienceand Technology Agency (JST) established in Izumi City. We got two competitive researchfunds (for ‘practical realization test’ and ‘development research for commercialization’)from JST. By that, we established high-volume production of L-10BPA and 10BHS, andobtained and accumulated numerous data for the production. Our experience of theindustry-academia-government collaboration and joint research in the Plaza Osaka served
as a base for making the highly reliable research proposal thereafter. In 2014, it also
became a driving force for constructing a laboratory base for boron agent development
aiming at medical realization of BNCT, and with the support of the Ministry of Economy,
Trade and Industry, the BNCT Research Center was established in Nakamozu Campus,
and the research activities continue to this day.

② “Message”

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NCT letter Issue 6 June 2019

It is said that BNCT has almost reached its medical realization, however, some issues are
yet to be solved. In the chemical and pharmaceutical area, development of a new boron
agent more effective than L-10BPA or 10BSH is the most important issue. Boron agentsfor BNCT differ from ordinary pharmaceutical agents in quality and behavior. The
traditional way of drug discovery, seeking new drugs from a number of boron compounds,
prevails at present, however, boronated molecular-targeted drugs and middle-molecular
drugs, and effective DDS are expected to be developed in the future. I yearn for young
researchers of the next generation to proceed with the research on boron agents from a
new perspective based on a steady basic research.

BNCT Research Center,
Osaka Prefecture University

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NCT letter Issue 6 June 2019

Hatanaka Award (18th ICNCT)“On receiving the Hatanaka Award”
Junichi Hiratsuka
Professor of the Department of Radiation Oncology,
Kawasaki Medical School
I was honored with the Hatanaka Award with the recommendation of the JSNCT membersin the 18th ICNCT. I would like to express my sincere gratitude. I believe that the basic
research and clinical studies I have done to the extent I can do have led to this award, andam now recalling the past with deep emotion.
In 1983, the late Prof. Yutaka Mishima of the Department of Dermatology, Kobe
University invited me to the “Research on development of nuclear reactor therapy bymetabolic activity of malignant melanoma” group of the Education Ministry’s Special
Research I. I was expected to conduct radiobiological study in relation to BNCT. It was
three years after graduation when I joined the group, and I was obliged to attend the groupmeeting (2 ~ 3 times per year). The discussions were difficult for me to understandthoroughly, but I remember I was drawn into the atmosphere of the seriousness andacademic discussions of the professors and doctors. At the first group meeting I attended(1984), discussion was made on the existence of BPA toxicity, existence of the selectivityof melanoma cells and systemic pharmacokinetics. ‘10B-chlorpromazine’ had been used
before BPA. Each time I see BPA being commonly administered at present, I recall thegroup meeting of those days. Among the members of those days were Professors Hidetake
Kakihana, Kazuo Yoshino, Keiji Kanda, Toru Kobayashi and Hiroshi Fukuda. As amember of the group, I started research on radiation biology. Since Prof. Fukuda had beenworking on cell experiments, I focused on animal experiments using pigs, hamsters andmice (Fig. 1). Under such circumstances, I was very surprised to see the reaction where ahuge naturally expressed melanoma in a pig disappeared by BNCT, and at the same time,
I decided to keep on involved in BNCT research/clinical practice into the future (Fig. 2).
In 1987, the world’s first BNCT using BPA was conducted in a case of melanoma
occurred in occipital subcutaneous layer (NCT-1) (nuclear reactor, Musashi Institute ofTechnology). It was very lucky for me to join the medical team then. Medical irradiation
has been continued thereafter and now the case number of the latest patient file in thebookshelf in my room is NCT-118 (treatment about 4 cases/year). Being involved in
BNCT made me learn a lot firsthand: ①clinical practice is built upon the downright base41

NCT letter Issue 6 June 2019of basic medicine; ②importance of teamwork; ③necessity of exchanging opinions with
doctors and professors of other areas; and ④importance of continuing research. BNCT
has a high potential. I look forward to continuing working together with the BNCT staff.
Especially I hope young researchers keep “importance of continuing research” in mind.
Finally, I would like to give my heartfelt thanks to everyone for supporting my research
activity. Thank you very much. I hope to continue working with you all.

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NCT letter Issue 6 June 2019

The Fairchild Award of the 18th International
Congress on Neutron Capture Therapy
Collimator Design of T/N-SPECT for BNCT
Saki Shibata
Division of Sustainable Energy and Environmental
Engineering, Graduate School of Engineering, Osaka
University
1. Introduction
One of the most important issues we should solve for BNCT is realization ofvisualization of the treatment effect (local dose) in real-time. The author’s group has beendeveloping a SPECT system to monitor the three-dimensional treatment effect during
BNCT, named BNCT-SPECT. The BNCT-SPECT can measure prompt gamma-rays of
478 keV emitted from residual excited 7Li nucleus via 10B(n,α)7Li reaction, in order toknow the treatment effect. In the present study, we develop a SPECT system to estimate
T/N ratio (10B concentration ratio of tumor to normal tissue) by measuring 2.22 MeV
gamma-rays emitted via 1H(n, γ ) reaction being normally a background signal, in
addition to measuring 478 keV gamma-rays. This system is called T/N-SPECT. The
present report describes design study results of the detection element and collimator of
the T/N-SPECT to be used in a very severe neutron background environment.
2. Calculation condition
Figure 1 shows the calculation model taking into account all the items existing in a real
irradiation room. We set the statistical accuracy as the estimation index considering (1)thickness of the detection element, (2) collimator length and (3) collimator radius. And
the image updating period was assumed to be less than 10 min. The T/N-SPECT was
designed to meet the statistical accuracy to be less than 5%. In the calculation, we
employed MCNP5 as a Monte Carlo transport code and estimated flux by F4 tally, flux
and reaction rate by F5 tally and gamma-ray pulse height spectrum by F8 tally. Other
conditions are as follows: The tumor size is 3cm in diameter, the head diameter is 20cm,
and the source is a 10 keV broad parallel beam of 15 cm in diameter. As the detection
element, a GAGG(Ce) scintillator was selected since it had a suitable energy resolution
and detection efficiency for T/N-SPECT.

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NCT letter Issue 6 June 2019

3. Calculation results
3.1 Thickness of detection element (GAGG)
With a typical calculation model like Fig. 1, thestatistical accuracy of the number of counts was
examined for the thickness of GAGG from 2 cm to 10
cm. As a result, for over 6 cm the statistical accuracy
did not change largely. This is because the detection
efficiency was saturated. From this, the thickness of thedetection element was fixed to be 6 cm.

Figure 1 Calculation model.

3.2 Collimator length
If changing the collimator length and/or collimator radius, the spatial resolution canaccordingly change. However, the spatial resolution is a crucial physical value, because
it should be required to meet the medical doctor’s query, i.e., less than 0.5 cm. In thepresent examination, we carried out calculations with variables of collimator length andspatial resolution. Besides, we set goals of the image updating period of less than 5 min.
and the statistical accuracy of less than 5 %.
Calculations were performed for collimator length from 25 cm to 65 cm and spatial
resolution from 3.5 mm to 6.5 mm. As a result, the best statistical accuracy was obtainedfor collimator length of 55 cm. Hence, the collimator length of T/N-SPECT was fixed to
be 55 cm.
3.3 Collimator radiusFigure 2 shows the statistical accuracies for the spatial resolution change as a functionof image updating period from 3 min. to 10 min. for the collimator length of 55 cm.
Designs to meet the statistical accuracy goal of 5 % were realized as in the following table.
Table 1 Final design results.
Spatial resolution (Collimator radius / length)
5.5 mm (4.57 mm / 55 cm)
6.0 mm (4.97 mm / 55 cm)
6.5 mm (5.37 mm / 55 cm)

44

Image updating period
9 min.
6 min.
4 min.

NCT letter Issue 6 June 2019

Figure 2 Relation of spatial resolution and statistical accuracy as afunction of image updating period for collimator length of 55 cm.

4. Summary
In the present study, we were finally not able to realize the design meeting all therequirements, i.e., statistical accuracy of less than 5 %, spatial resolution of less than 5
mm and image updating period of less than 5 min. However, the obtained designs mostly
reached the requirements, which could still be available depending on the medical
doctor’s query. In the next step, we will try to develop a prototype detector and examine
the performance by experiments.
Acknowledgement
Finally, the author would like to express her sincere gratitude to Prof. Isao Murata for
his encouragement of preparation of the presentation for the Conference, and to Prof.
Itsuro Kato for his having given a chance to me to submit a report to NCT l

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NCT letter Issue 6 June 2019

The Fairchild Award of the 18th International Congress on Neutron
Capture Therapy
Development of a prompt gamma ray imaging
detector using LaBr3(Ce) scintillator and arrayed
MPPC for boron neutron capture therapy
Keita Okazaki1, Kiyotaka Akabori2, Takushi Takata3,
Yoshinori Sakurai3, Hiroki Tanaka3
1
Graduate School of Engineering, Kyoto University, 2Sumitomo
Heavy Industries, Ltd., 3Institute for integrated radiation andnuclear science, Kyoto University
Introduction
To evaluate the prescribed dose of BNCT, it is necessary to obtain 10B concentration inblood, normal and tumor tissues. In general, the information on 10B concentration in blood
has been acquired by ICP methods or a high purity germanium detector at KUR before
the treatment. However, these procedures cannot measure 10B concentration in real time.
It is required that the information on 10B concentration is obtained in real time to evaluate
the prescribed dose during the treatment. Thus, we have been developing a prompt
gamma-ray imaging detector that consisted of a slab of LaBr 3(Ce) scintillator and an 8 x
8 array multi-pixel photon counter (MPPC). In this paper, we report the characteristics ofour detector system.
Materials and methods
Our detector system was composed of a slab of LaBr3(Ce) scintillator which was 50 mm
x 50 mm x10 mm, an 8 x 8 array MPPC, an amplifier unit, a shaper, and an ADC. An
MPPC can detect the scintillation light from this scintillator, and amplified signals send
to a PC. Lastly, we can get 64 channels’ gamma-ray spectra on a PC. During experiments,
we set up operating voltages to adjust each gain of an MPPC. First of all, the energy
resolution for the 511 keV gamma-ray peak was evaluated with a source of 22Na. In
addition, we obtained 64 gamma-ray spectra when thermal neutrons irradiated samples
loaded with boric acid whose concentration was 50 and 5000 ppm. The thermal neutron
flux was 1.0 x 105 n/cm2/s at 1 MW.
Results46

NCT letter Issue 6 June 2019

The energy resolution for the 511 keV peak was 5.7 % on average. This energy
resolution was sufficient to discriminate between 478 and 511 keV gamma-ray peaks.
The 478 keV peak overlapped the 511keV peak, but we discriminated between the two
gamma-ray peaks by defining two Gaussian distributions for each gamma-ray. After theelimination of the effect from 511 keV peak where the peak overlapped the 478 keV peak,
we got the two-dimensional distribution of 478 keV gamma rays.
The impression of this conference
I learned lots of research that were performed in other countries through this conference,and I discussed my research topic with other researchers. This meeting was extremely
wonderful. This meeting had a get-together where we could have a traditional dinner.
This is my incentive to continue my research; thus, I will attend international conferences
proactively.
I would like to appreciate Prof. Fong-In Chou giving me the Fairchild ward. Also, I
appreciate Dr. Kato giving me this opportunity to write this article.

The ceremony

Members of my laboratory at banquet

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NCT letter Issue 6 June 2019

Recipient of the Fairchild award at the 18th International Congress on
Neutron Capture Therapy
Neutron beam quality measurement of an acceleratorbased neutron source using microdosimetric technique
Naonori KO1, Ryohei UCHIDA1, Keita OKAZAKI1,
Takushi TAKATA2, Hiroki TANAKA2, Yoshinori
SAKURAI2
1
Graduate school of Engineering, Kyoto University
2
Institute for Integrated Radiation and Nuclear Science, Kyoto University
Introduction
An accelerator-based neutron source is gaining interest due to its ability to perform
treatments, such as BNCT in a hospital environment. Currently, many facilities aretrialling accelerator based BNCT. The accelerator-based neutron source at Aomori
prefecture Quantum Science Center (QSC) is primarily used for cell and small animalstudies. In a typical BNCT field, there exists many different types of radiation with eachhaving a different biological effect. To maximise the treatment efficiency, it is importantto understand the beam quality of the neutron source. Microdosimetry is a technique used
to measure radiation in a mixed field. Using this technique, it is possible to derive therelative contributions of each radiation component. A tissue equivalent proportionalcounter (TEPC) measures energy deposition in a simulated micrometer scale volume
comparable to that of a living cell. The TEPC uses material and gases that are essentiallyequivalent to human tissue in chemical composition. This study aims to measure themicrodosimetric quantities of an accelerator-based neutron source utilised for BNCT
research using a tissue equivalent proportional counter (TEPC). The experimental dataobtained with the TEPC was also compared against Monte Carlo simulation.
Material and method
The accelerator-based neutron source at QSC consists of a 20 MeV proton beam anda beryllium target. A moderator system was designed to slow down the fast neutroncomponent to increase the thermal neutron flux. The microdosimetric spectrum wasmeasured using the Far West Technology Inc. LET 0.5 inch TEPC. The counter was filledwith a methane-based tissue equivalent gas at a pressure of 74.5 hPa to simulate a 1 mdiameter sphere. The neutron beam was measured at the centre of the field using the TEPC
during approximately one hour in a free-air condition
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NCT letter Issue 6 June 2019

Results
The absorbed dose from events exceeding 20 keV/m measured free in air for a onehour irradiation was calculated as 1.310.02 Gy. The simulated results were
1.410.07 Gy. The measured and calculated values exhibit good agreement. The relative
biological effectiveness (RBE) that was evaluated from the measured microdosimetric
spectrum was calculated as 3.70.02, similar to the simulated value of 3.80.1.
Conclusion
The microdosimetric spectrum of the QSC accelerator-based neutron source was
successfully measured. The results showed the PHITS Monte Carlo simulation cansimulate both micro and macrodosimetric quantities accurately.
My experience at the 18th ICNCT in Taiwan
This was my first time presenting at the ICNCT. I had the opportunity to meet many
researchers and exchange valuable ideas. The scientific sessions were interesting andextremely educational, and I am very grateful to my supervisors for supporting me.
Finally, we would like to thank the president of the 18 th ICNCT, Prof. Fong-In Chouand the selection committee members for selecting myself as one of the recipients of the
Fairchild award. In addition, we would like to thank Dr. Itsuro Kato for offering us theopportunity to publish our work in this letter.

Figure 1.

Members of the research lab at theInstitute for Integrated Radiation and Nuclear Science. (Author: Far right)
49

NCT letter Issue 6 June 2019

Figure 2. Strange dancing dollthat appeared at the banquet.

50

NCT letter Issue 6 June 2019

Article-introduction of the topic
1. <Biology >Title: Eosinophil depletion suppresses radiation-induced small
intestinal fibrosis
Authors: Naoki Takemura, Yosuke Kurashima, Yuki Mori, Kazuki Okada, Takayuki
Ogino, Hideki Osawa, Hirosih Matsuno, Lamichhane Aayam, Satoshi Kaneto, Eun
Jeong Park, Shintaro Sato, Kouta Matsunaga, Yusuke Tamura, Yasuo Ouchi, Yutaro
Kumagai, Daichi Kobayashi, Yutaka Suzuki, Yoshichika Yoshioka, Junichi Nishimura,
Masaki Mori, Ken J. Ishii, Mark E. Rothenberg, Hiroshi Kiyono, Shizuo Akira, Satoshi
Uematsu
The source: Science Translational Medicine, 2018 Feb 21;
10(429)https://stm.sciencemag.org/content/10/429/eaan0333/tab-pdf

Presented by Lichao Chen (Department of Frontier Life
Sciences, Nagasaki University Graduate School of
Biomedical Sciences)
2. <Medicine >Title: Boron neutron capture therapy for high-grade skull-basemeningioma
Authors: Koji Takeuchi, Shinji Kawabata, Ryo Hiramatsu, Yoko Matsushita, Hiroki
Tanaka Yoshinori Sakurai, Minoru Suzuki, Koji Ono, Shin-Ichi Miyatake, Toshihiko
Kuroiwa
The source: Physics in Medicine & Biology (2017) 62: 4421- 4439
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133692/

Presented by Yusuke Fukuo (Department of
Neurosurgery and neurovascular therapy, Osaka
Medical College Hospital)
3. <Physics>
Title: Fast neutron dose evaluation in BNCT with Fricke gel layer
51

NCT letter Issue 6 June 2019detectors
Authors: G. Gambarini, G. Bartesaghi, J. Burian, M. Carrara, M. Marek, A. Negri, L.
Pirola, L. Viererbl
The sources: Radiation Measurements 45 (2016) 1398-1401
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100278/

Presented by Yuto Murakami, et al (Graduate School of Engineering,
Hiroshima University)
4. <Pharmacology>
Title: Design, synthesis, and evaluation of lipopeptide conjugates of
mercaptoundecahydrododecaborate for boron neutron capture
therapy
Authors: Aoi Isono, Mieko Tsuji, Yu Sanada, Akari Matsushita,
Shinichiro Masunaga, Tasuku Hirayama, and Hideko Nagasawa
The sources: ChemMedChem (2019) 14 : 823-832
https://chemistry-europe-onlinelibrary-wileycom.remote.library.osakau.ac.jp:8443/doi/full/10.1002/cmdc.201800793

Presented by Kazuki Kawai (Laboratory for Chemistry and Life Science
Institute of Innovation Research, Tokyo Institute of Technology)

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NCT letter Issue 6 June 2019

Editor’s Postscript

On the Publication of NCT letter Vol. 6

Chief Editor of NCT letter
Itsuro Kato
The 2nd Department of Maxillofacial Surgery, Graduate School of
Dentistry, Osaka University
I would like to take this opportunity to wish every success to all of the members of theJapanese Society of Neutron Capture Therapy (JSNCT). We could publish the NCT letter
No. 6 supported by the all of contributors. The members I worked with for the NCT letter
were Prof. Mitsuko Masutani of the department of Frontier Life Sciences, Nagasaki
University Graduate School of Biomedical Sciences and Dr. Teruyoshi Kageji of thedepartment of Neurosurgery, Tokushima Prefectural Kaifu Hospital as editors and Prof.
Hideki Matsui of the department of Physiology, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences as an advisor. This time also we sought
advices from Prof. Hiroyuki Nakamura, the president of this Society.
The number of pages of NCT letter No. 6 was increased compared with that of No.5,
because both manuscripts of awardees of BNCT related conferences and those whose
reports BNCT related topic in the conference which is unrelated to BNCT were increased.
It means that the activities of JSNCT members were evaluated at domestic and foreignsocieties. Prof. Matsumura reported that BNCT session had been picked up as a major
symposium at American Association of Cancer Research (AACR) 2019 at US as written
in P 22. And Dr. Hirose, K. in Southern Tohoku BNCT center had presented “Safety andantitumor activity of accelerator-based BNCT in patients with inoperable recurrent andlocally advanced head and neck cancer. -A phase II study” at poster session in American
Society of Clinical Oncology (ASCO) in 2019, 5/31-6/4 at Chicago, whose report was
not written in this letter.
I expect and wish every success to all of the members of JSNCT.
I will try to send an activity of all member to foreign countries as much as possible atreal time, through linking HP of International Society of Neutron Capture Therapy(ISNCT) to that of JSNCT.
I want to take up the media news, the transfer of the member, a new plan, an article
about BNCT including the contribution to this letter desired widely. I am happy if I cangive frank opinion, information of members to me. Thank you for your cooperation.
53