NEWSLETTER OF

ISSUEJAPANESE SOCIETY OF

1

NEUTRON CAPTURE
THERAPHYMay2016

NCT News
this issue
Cancer Therapy: A new horizon P.1
Topic: The accelerator-driven BNCT facility atSouthern TOHOKU General Hospital P.2
Report of the 12th Congress P.6

The Solution forCancer

Events & News P.8

Over the course of mankind’slong history, cancer has proved
to be its greatest enemy. Now
we have a chance to overcome
this foe. BNCT integrates thearts of medicine, pharmacy andphysical technologies, and weneedtoconsolidate

ourcapabilities in all these fields.

Cancer Therapy: A new horizon
It is my great honor and privilege to be thepresident-elect of the Japanese Society of Neutron
Capture Therapy (JSNCT), succeeding Prof Junichi
Hiratsuka and Prof Koji Ono as of September 2015.
Boron Neutron Capture Therapy (BNCT), which
previously used nuclear reactors, has reached amajor turning point since the world’s firstaccelerator-driven BNCT (A-BNCT) facility wasdeveloped in Japan in 2010. The Phase I A-BNCT
clinical trials for treating brain tumors are almost
complete, and preparations are being made for thephase II study for head and neck cancer - similar tothe phase I trials. In addition, several plans forenhancing A-BNCT are ongoing in universities andhospitals. Under these circumstances, in order topursue a policy of combining basic research andclinical studies, and promoting industry–academia
partnerships, as well as further promoting BNCTstudies, I would like to announce three principal
strategies as listed below, all of which will beimplemented for the further developmentof Society:
1. Cultivating BNCT specialists and developing
information-sharing protocols
2. Developing new drugs for efficient borondelivery
3. Disseminating the information obtained acrossthe world
During the past four years, three lecture courses
were held as part of the JSNCT training program for
BNCT specialists. Since it is particularly importantto cultivate BNCT specialists, including JSNCTcertified doctors, we will continue our work to
educate people to a high level of competency in thisfield. We will also strive to promote information
sharing among these specialists through thetraining programs.

This year we inaugurated the Mishima Memorial
Award for Chemistry to be presented to anoutstanding researcher in clinical studies drug
development. The first Award was given to Dr.
Kazuo Yoshino.
One urgent issue in BNCT is the development ofa new boron agent that can ensure further
progress in the field. The two agents currently
used were synthesized about 60 years ago.
The JSNCT is also constantly encouraging
researchers to develop new drugs. We must unite
basic research with clinical studies. Available
resources should be devoted to the developmentof new drugs through industry–academia
partnerships. We must also establish a standard
procedure for evaluating the drugs developed, sothat we can initiate translational research.
It is extremely important to disseminate thecorrect information across the world. We will thenbe able to establish an international standard for
BNCT treatment. I believe this JSNCT Quarterly
Newsletter will serve an essential role in thispurpose.
As the president of JSNCT I will put great effort
into realizing BNCT therapy for all cancer
patients.

Hiroyuki Nakamura, P h DPresident
J a p a n e s e S o c i e t y o f Neutron Capture Therapy
Professor
Tokyo Institute of TechnologyNCT News 1

May 20161

Topic: The accelerator-driven
BNCT facility at Southern
TOHOKU General Hospital
The world’s first BNCT hospital

Introduction
The Southern TOHOKU General Hospital was establishedin 1981 as the Southern TOHOKU Research Institute (STR)
mainly catering for neuroscience in Fukushima prefecture,a south eastern region of the Main Island, Japan. Now 34
years on we have 80 healthcare organizations and 5
general hospitals under the same headquarters. Figure 1
shows an overview of our main facilities in Koriyama city.
The mission statement of the STR is 'Japanese excellence
for health and hope'. In order to achieve this mission, weintend to provide advanced new technologies and medical
treatment protocols. Currently the standard cancer
treatments are surgery, radiation therapy and chemotherapy.
We have a substantial range of equipment for diagnostic
imaging: five instruments for Positron Emission
Tomography/Computed Tomography (PET-CT), six for
Magnetic Resonance Imaging (MRI) and six for CT. The
STR is equipped with cutting-edge radiation treatment
systems: a linear accelerator, a remote after-loading
system, a Gamma Knife, a CyberKnife and a proton-beamtherapy treatment system including two rotating gantry
irradiation rooms and one horizontal irradiation room. The
STR, in addition, provides two hyperthermia systems, two
hyperbaric oxygen therapy systems and an immunotherapysystem. The STR actively embraces advanced medicalcare by introducing diagnostic and treatment methods for
all cancer types.

J Chadwick discovered the neutron in 1932. Soon after thediscovery, GL Locher suggested the basic idea for using theneutron capture reaction for treating cancer in 1936. The
first BNCT clinical trial for malignant tumors was performed
in 1951 by WH Sweet. However, because of inadequacies
in the boron agent and neutron flux, most of these trials
failed.
H Hatanaka in Japan began BNCT clinical trials for brain
tumor treatments in 1968. Boron compounds and neutron
flux have gradually improved since. A key requirement for
BNCT is a neutron source. At first reactors were used,although installing the BNCT system is prohibited by law inmost hospitals. In 2008 an accelerator-driven neutron
facility was inaugurated at Kyoto University Research
Reactor Institute (KURRI) by Sumitomo Heavy Industries,
Ltd. The first clinical trial for brain tumor therapy wasperformed in 2012 using the KURRI facility.

Southern TOHOKU BNCT Research Center
In June 2012 the STR decided to install an acceleratordriven BNCT as a novel modality for cancer patients andconstruction began in March 2013. The first acceleratordriven BNCT Research Center in the world was establishedin September 2014 (Figure 2). The BNCT facility wascommissioned and completed in February 2015 andopened as a medical facility in November 2015, and the firstclinical trial at the Southern TOHOKU BNCT ResearchCenter was performed in the beginning of 2016 for a patientwith a brain tumor.

Medical clinic

Headquarters

ProtonTherapy
CenterBNCTResearchCenter

Second hospital

Figure 1. Panoramic view of the Southern TOHOKU Research Institute (STR).
(http://www.minamitohoku.or.jp/english/)

NCT News 1May 20162

The setup at Southern TOHOKU BNCT ResearchCenter
The BNCT facility consists of a cyclotron-driven neutron
source (C-BENS), a measurement system for blood boron
levels and a transportation system for the patient. The CBENS was developed with the cooperation of KURRI andSumitomo Heavy Industries. The C-BENS was installed atthe BNCT Research Center in April 2014.
The BNCT system is located on the basement floor of theSouthern TOHOKU Research Center where we have amachine room for the C-BENS, a room for Inductively
Coupled Plasma (ICP) analysis, two preparation rooms andtwo treatment rooms (Figure 3).
The C-BENS machine consists of a cyclotron, a beamtransport system, a beam-shaping assembly and acollimator assembly. The wall of the cyclotron room is 2.5 m
thick for radiation protection.

Figure 2. Southern TOHOKU BNCT Research Center

The ICP analysis room is used for measuring theconcentration of boron in blood. The transport system, whichtransfers patients from the preparation room to the treatment
room, is equipped with radiation protection.

(b) Treatment room(a) Floor design(c) Preparation room(e) ICP analysis room(d) Cyclotron room

Figure 3. Layout of the Southern TOHOKU BNCT Research Center

NCT News 1May 2016

3Cyclotron: HM-30

Collimator assembly

The cyclotron HM-30 is compact in size, with a width of 3.0m, length of 1.6 m and height of 1.7 m. It accelerates
negative hydrogen ions to 30 MeV, and produces a proton
beam of more than 1 mA. Note that this proton beam isextracted by a carbon foil stripper. The HM-30 can be
operated for 1 hour at 1 mA in a stable manner, which
suffices the requirements for its use in medical treatments.

The proton beam is injected into a target of beryllium platefor generating neutrons. The aperture diameter of thecollimator for the neutron beam ranges from 100 mm to 250mm. The collimator, which is made of polyethylene
including 50 wt% of lithium fluoride, is placed in theneighborhood of the patient.

Beam shaping assembly (BSA)The extracted proton beam is expanded by two scanner
magnets in order to moderate the concentration of heat on
the beryllium target, which is directly cooled by water toremove the heat flux of 30 kW. The neutron flux emitted ismoderated by moderator equipment made from lead, iron,aluminum and calcium fluoride (Figure 4).
The BSA is surrounded by blocks of lithium-fluoride-loaded
polyethylene and low-activation concrete to reduceradioactive effects caused by the thermal neutrons. The
concrete wall is further shielded by 1 cm thick silicone
rubber, which contains 20 wt% of B4C.
In order to reduce workers’ exposure to additional γ-rays
from the activated moderator, movable Pb shields with athickness of 4 cm are installed.
The reaction between 30 MeV protons and the beryllium
target emits high-energy neutrons, up to 28 MeV, in thebeam direction. The BSA can reduce the neutron energy
dissipated into the epithermal energy region because leadand iron work as moderators with inelastic cross-sections,and aluminum and calcium fluoride work as shapermaterials. The resulting spectra of the neutron beam are in
the range of several tens of keV.
The BSA is designed to obtain a sufficient intensity ofepithermal neutrons and to reduce contamination by γ-ray
and the dose from fast neutrons.

A series of tests for neutron generation started in
September 2014, and were completed in February 2015.
Various irradiation characteristics were evaluated such as
the whole-body exposure to a patient, the reduction ofexposure for workers, and the performance of the BSA.
Biological characteristics were also checked using tests oncells.
In order to validate the results of Monte Carlo simulations(MCNPX), irradiation tests were performed using multi-foils
for detecting high-energy neutrons ranged over a few MeV,
and by using a water phantom for detecting thermal neutron
distribution.
It was concluded that the simulations for reaction rates
caused by high-energy neutron and thermal neutron
distributions in a water phantom agreed well with themeasurement results. The peak flux on the maximum
collimator size (25 cm in diameter) in the water phantom
was confirmed at about 1.8×109 neutrons/cm2/sec at a
depth of 20 mm from the surface under the 1 mA protonbeam. The measured thermal distributions on the reference
collimator size (12 cm in diameter) in a water phantom
correspond well with the calculated results (Figure 5).

Transportation system of patient
The transportation system for patients is newly developed
to reduce the working time in the treatment room. Note thatworkers cannot come into the treatment room just after
irradiation therapy because of the remaining radioactivity.

LiF-loaded polyethylene

PbProton beam(30 MeV)FeCaF2

AlFigure 4. Schematic diagram of the beam shaping
and collimator assembly

NCT News 1

May 20164Figure 5. Thermal neutron distribution in a water phantom
on the center axis. The collimator size is 12 cm indiameter, which is our reference collimator size.

Technology Solution

Measuring system of boron concentration in bloodby ICPIn the ICP analysis laboratory room we provide two ICPEmission Spectrometers for measuring the boron
concentration in the blood. It is extremely important tomeasure the boron concentration, because it is used todetermine the irradiation time.

Medical team for BNCT treatment
Clinical BNCT treatment requires a team of physicians,including internal medicine, surgery, radiation therapy,
radiology diagnostics, radiation oncology, and pathology,
with other healthcare professionals on standby. The teammembers meet to discuss the best therapy for the patient,select and combine treatments, and finally determine apersonalized therapy program for each patient. We firmly
believe that this system provides the right medical
treatment for the patient.

Further scope of BNCTIn the near future the BNCT will benefit from combining withother treatments such as surgery, radiotherapy,
chemotherapy and target therapy including immunotherapy(see Figure 6). This procedure will be standardized forpatients with primary tumors.

Figure 6. Combined modality therapy

NCT News 1May 2016

5

Report of the 12th Congress
The 12th Congress of JSNCT washeld at Kobe Gakuin University
during September 4 and 5.

Prof. Hideki Ichikawa of Kobe Gakuin University organized the 12th Congressof JSNCT during September 4 and 5, 2015. The Congress was held at thebeautiful campus of the University in Kobe Port Island.
The cover pages of the proceedings are blue and green, which are a symbolof Seto Inland Sea surrounding the Port Island and the well-kept lawn at theUniversity campus.
The thematic words of the Congress were “The upcoming Boron Neutron
Capture Therapy”, and Prof Ichikawa introduced three main subjects: 1)
development of accelerator-driven neutron generators, 2) clinical application ofBNCT and 3) development of drugs for boron delivery.
The total number of participants was 250. More than ten members from Taiwan- mainly from National Tsing Hua University and Taipei Veterans General
Hospital - joined and presented their works.

Prof Hideki Ichikawa inaugurating
the opening address

The proceedings

Educational lecture given byProf Koji Ono

The former President Prof Jun-ichi
Hiratsuka and Dr Kazuo Yoshino, thewinner of Mishima Memorial Award forChemistry.

At the gala dinner party

NCT News 1

May 20166

During the Congress there was one educational lecture,
two plenary lectures, three work-shop presentations, twoluncheon seminars, thirty oral presentations, and twentythree poster presentations, that is, all together sixty-twolectures and presentations.
Prof Emeritus Koji Ono of Kyoto University, the founder ofJSNCT, presented an educational lecture under the title of“Perspectives of BNCT research from CBE (CompoundBiological Effectiveness) analysis, and Prof Minoru Suzuki
presented “Accelerator-based BNCT and clinicalapplication.”
Dr Kazuo Yoshino of Shinshu University was commended
for the Mishima Memorial Award for Chemistry on thesecond day of the Congress, and as awardee presented
the results of his research.

Delegates from Taiwan at the dinner party

The following lectures presented also drew attention:

 Prof Mitsunori Kirihata of Osaka Prefectural University:“Development of low molecular weight boron agent andthe perspectives of the agent”
 Dr Chikako Shikata of the Regulatory ScienceFoundation: “Process for development and approval of
medical drugs in Japan”
 Prof Hiroyuki Nakamura of Tokyo Institute of Technology:“What are the obstacles for development of new borondrug”.

Scoring at the gala dinner party

Prof Hideki Matsui of Okayama University, as therepresentative of JSNCT, presented a report to the visiting
IAEA (International Atomic Energy Agency). He met andexchanged information with the IAEA experts who are in
charge of BNCT, that is, Dr. Meera Venkatesh, Director of
the Division of Physics and Chemical Sciences, and theDepartment of Nuclear Sciences and Applications (NA),and Dr. Ahmed Meghzifene, Head of Dosimetry and the
Medical Radiation Physics Section. Note that IAEA is theorganization responsible for all radiation therapies.

Poster session

Prof Matsui said that at IAEA he showed the detailed statusof research and development of BNCT in Japan both forthe accelerator-based neutron facilities and for boron
agents, which attracted great attention from IAEA experts.
Both organizations - JSNCT and IAEA - agreed to continue
to exchange. Dr. Meghzifene requested that Prof Matsuijoin an international conference on BNCT to be held in2017.
After the first day of presentations a gala dinner party was
held, and participants fully enjoyed the famous milliondollar night view of the Kobe port.

Report for visiting IAEA given by Prof Hideki Matsui anddiscussions

NCT News 1May 20167

Events & News• Phase I clinical trial using the accelerator-based neutron source (ABNS) was completed
for recurrent malignant gliomas (GBM)

Professional
Development
We now stand on the brink

BNCT clinical studies using the reactor-based neutron source were mostly completed by 2012. Anotherpossibility is to use the accelerator-based neutron source (ABNS). ABNS is in the process ofdevelopment for applying BNCT under hospital settings. Sumitomo Heavy Industries has produced asmall size of ABNS facility in collaboration with Stella Pharma. A cyclotron (C-BENS) is used forgenerating the proton beam. A Japanese group has just successfully finished the case registration of thephase I clinical trial by using the C-BENS system for recurrent malignant gliomas (GBM). They now plan
to start the phase II clinical trial by using the same system under the same clinical entity. (Reported byProf Shinichi Miyatake, Osaka Medical College)of a new stage in theclinicalapplicationofBNCT. It is important we
cultivate our capabilities
withnodiscrimination

based on gender, since theBNCT requires

all theabilities of a diverse set ofprofessionals.

• The next congress of JSNCT for the year of 2016 will be held in Tokyo
Prof Hironobu Yanagie, Meiji Pharmaceutical University, will organize the 13th Congress of JSNCT in
2016. It will be held on August 6th and 7th, 2016 at the Ito Hall of Ito International Research Center at
Hongo Campus, the University of Tokyo. In association with the Congress the 4th lecture meeting for theBNCT technologies will be held in the evening of August 5th at the same venue.

• Nagoya University introduced an accelerator-driven neutron facility
A compact neutron facility that provides a low-energy high-current DC accelerator (IBA Dynamitron;
2.8MeV, 15mA proton beam) was introduced in September 2015 at Nagoya University for use in theapplication of BNCT. The target is made from Li, which uses the 7Li(p,n)7Be reaction. The output neutron
flux will be moderated by a compact beam-shaping assembly (BSA). The low-energy protons incident
on the lithium target may be suitable for the accelerator-driven BNCT. However, the lithium target involves
several difficulties (i.e., low melting point, high chemical activity and 7Be production). A new sealed Li
target will be developed for pursuing easy and safe maintenance work. (Reported by Prof Kuzuki
Tsuchida, Nagoya University)

Editor: Hideki MATSUI; Professor, MD, PhD
Department of Physiology
Graduate School of Medicine & Dentistry, Okayama University
2-5-1 Shikata, Okayama, 700-8558 Japan
E-mail: matsuihi@cc.okayama-u.ac.jp, Phone: +81-86-235-7104

Japanese Society ofNeutron Capture Therapy
NCT News 1May 20168