BORON NEUTRON CAPTURE THERAPY FOR CANCER: FUTURE

PROSPECTS IN INDONESIA
Bagaswoto Poedjomartono1, Hanif Afkari1, Edy Meiyanto2, Yohanes Sardjono3
1
Radionuclear services, Department Radiology of RSUP Dr. Sardjito /
FKKMK- Universitas Gajah Mada, Yogyakarta
2
Faculty of Pharmacy, Universitas Gajah Mada, Yogyakarta
3
PSTA BATAN Babarsari, Yogyakarta

Abstract Boron Neutron Capture Therapy (BNCT) for cancer therapy is based on interaction of low energy of
thermal neutron and Boron-10 (10-B) to produce alpha radiation from He-4 and Li-7 with a high linier energy
transfer. The results in a lethal radiation dose to tumor cells when beem of neutron interact with tumor seeking
boron labelled drugs limited in the cells cancer, such as boron sodium captate (BSH), borophenyllalanine
(BPA) for brain tumor or Pentagamaboronon-0 (PGB-0) for breast cancer. The last drug is still in research in
Faculty of Pharmacy Universitas Gadjah Mada Yogyakarta. The irradiation of alpha He-4 and LI-7 from B-10
which is radiated with thermal neutron occurs only in tumor cells while healthy cells are relatively safe. In
Indonesia BNCT therapy is currently a topic to be discussed and is expected to be used to kill cancer cells
better than the way used today.
Keywords Cancer, BNCT, Targeting Therapy, PGB-0

INTRODUCTION 9-14 micrometers while the cell size is between 10-

An Ideal cancer therapy is a non invasive
therapy that can kill cancer cell specifically
without damaging normal cells around it and
does not provide severe side effects. In general,
cancer therapy performed at this time is a
combination of surgical procedures,
chemotherapy and radiotherapy. However, these
three types of cancer therapies still have high
side effects. Therefore, now a relatively more
effective method of cancer therapy is developed
which is known by the name Boron Neutron
Capture Therapy (BNCT). BNCT is a nuclear
reaction based therapy that occurs when B-10 is
irradiated with low energy neutrons to produce
high energy alpha particles from Helium (He-4)
and Lithium (Li-7). As a cancer therapy, BNCT
has more advantages than chemotherapy. The
administration of chemotherapy drugs only kill
cancer cells that are actively dividing, but the
alpha particles has the ability to damage tumor
cells that are not dividing (Barth et al. 1990).
This alpha particle has a very short range, only
20 micrometers, so that the radiation only occurs
within the tumor cells. Consequently, the normal
cells near the tumor site are relatively safe ( Barth
et al. 1990).
For brain tumors, BNCT therapy is performed
by giving B-10 with BSH or intravenous BPA to
localize the tumor. In Indonesia, the PGB-0 is still
under development which B-10 is mixed with
curcumin analogs to be used for breast cancer
therapy with positive molecular markers of HER2.
CANCER
In 2012, There were approximately 8.2 million
deaths caused by cancer especially lung cancer,
liver, pancreas, colorectal, and breast cancer which
were leading cause of death every year. Smoking is
a main risk factor to cancer, while the other risk
factors include high body mass index (BMI), lack
of consumption of fruits and vegetables, inactivity,
and excessive consumption of alcohol. It is
estimated that the annual cancer cases will increase
from 14 million in 2012 to 22 million in the next
two decades (Kemenkes, 2015).
Based on GLOBOGAN (IARC) 2012, breast
cancer was a cancer with the largest percentage
of new cases, which was 43.3% with a
percentage of deaths of 12.9%. Lung cancer was
the type of cancer with the highest number of
new cases and the leading cause of death on
male populations. However, lung cancer also
had a high percentage in women, which was
13.6%, with a mortality rate of 11.1%. Liver
cancer had a relatively equal percentage of
mortality on both male and female populations.
Breast cancer and prostate cancer have a much
lower percentage of deaths than the percentage
of new cases, so if the cancer can be detected
and treated early then the chances of recovery
will be higher (GLOBOGAN, 2012). Based on
pathology-based registration, the relative
incidence of breast cancer reaches 11-12 new
cases per 100,000 at-risk population (WHO,
2014; Asamris et al., 2010; Wahidin et al.,
2012). Indonesia has a prevalence of cancer for
all ages in 2013 of 1.4%o, or an estimated
347,792 people. The Province of Special Region
of Yogyakarta had the highest incidence of
cancer Indonesia in 2013 of 4.1%o with
estimated absolute number of 14.596 people
(Riskesdas, 2013). Cervical and breast cancer
had the highest prevalence in Indonesia in 2013,
cervical cancer by 0.8%o and breast cancer by
0.5%o, while the highest prevalence of cervical
cancer is 1.5%o and breast 2.4%o in
Yogyakarta.
BORON NEUTRON CAPTURE THERAPY
Boron Neutron Capture Therapy (BNCT)
was introduced in the 1960s, but showed little
progression, because the thermal and epithermal
neutron sources were not economical. Nuclear
reactor, with a cyclotron was used recently as a
source of neutrons, thus enabling the usage
widely (Barth et al. 1990). Gamma rays are used to
irradiate tumor tissue, and fractional doses of up to
50-60 Gray are needed for tumor ablation in
conventional radiation therapy. This high dose of
radiation not only damages the tumor cells but also
harms the surrounding normal tissues. BNCT is
intended to eliminate side effects from
conventional radiation therapy. Basically, BNCT
internalize 10-boron into tumor which is irradiated
by 1 neutron, resulting in the insertion of 7 lithium
and 4 alpha particles into tumor cell which has
lethal energy to kill tumor specifically (10B + 1 n
→ 7 Li + 4 He + 2.31MeV (93.7%) or 10B + 1 n
→ 7 Li + 4 He + 2.79MeV (6.3%)). The ions and
particles of lithium are particles with high linear
energy transfer (LET), which produces a
considerable biological effect.
BNCT is a two-component modality, where the
enriched 10B compounds are given before
irradiated with thermal neutron rays. The 10-B
absorbs neutrons and releases alpha particles from
the nucleus (4He) and lithium (7Li). Because this
product has the reach only 5-10 micrometers in
water, the effect depends on maintaining a
relatively high 10-B concentration in the tumor
compared to the surrounding normal tissue. Only
tumor cells that absorb 10-B are destroyed.
The short range of alpha particles in the tissue
(5-10 micrometers) limits cell damage, because
radiation only occurs in cells that absorb boron
atoms (Yanagie et al. 2009). Boron phenyl alanine
(BPA), sodium boronocaptate (BSH), and the
molecule used by our team, namely BoronoDeoxy-
D-Glucose (BDG), are used to target boron into
tumor tissue. BNCT is primarily intended to be
used for the treatment of neck and head cancers
due to technical difficulties and economical
burden. However, the recent technical
improvements in BNCT applications have led to
this technique being considered for the treatment of
soft tissue tumors such as breast cancer (Akan et
2
al. 2014). damages and also fertility problems. Yet, there are
Breast cancer is the most commonly also many people who do not have long-term
diagnosed cancer for female. Recurrent breast problems from chemo. The side effects of chemo
cancer (RBC) is potentially threatening have to be considered to needs to kill cancer cells.
women’s life. Even though radiation therapy is
common to do, this therapy has several side Normal cells that are most likely damaged by
effects and is not potent enough to be used in chemo are:
RBC patients. Recently, BNCT is introduced in • The blood-forming cells in the bone
the medical field as an alternative treatment for marrow
cancer. The successes in in-vitro studies and • Hair follicles
simulations have led scientists to prepare
• Cells in the oral cavity, gastrointestinal
successful clinical outcomes in the future
tract, reproduction system.
(Menichetti et al. 2009; Horiguchi et al. 2011).
To maximize the potency of BNCT, it requires a
Some drugs can damage the cells of the heart,
proper combination of thermal/epithermal
kidneys, bladder, lungs, and nervous system.
neutron fluctuation which is related to the
Sometime, other drugs are given alongside chemo
selective 10B intake in target tissue. With the
drugs to protect the healthy or normal body cells.
new boron carrier design and neutron source,
There are also treatments to help alleviate side
BNCT can play an important role in treating this
effects.
malignancy, either primary or recurrence
Doctors try to give chemo at high enough level
cancer, because until now there has been no
to treat cancer, while maintaining minimal side
effective therapy to treat cancer.
effects. They also try to avoid the use of drugs that
have similar side effects (American Cancer
CHEMOTHERAPY’S ADVERSE EFFECTS
Society, 2016).
Chemotherapy is the process of inserting
Many side effects disappear quickly, but some
drugs through veins into the body. This method
may take months or even years to completely
makes the level of drug concentration in the
disappear. Sometimes side effects can last a
center of the tumor and other tissues the same.
lifetime, such as when chemo causes a long-term
Thus, chemotherapy can damage a variety of
damage to the heart, lungs, kidneys, or
healthy organs, not just diseased body tissues. It
reproductive organs. Certain types of
causes some side effects such as; decreased of
chemotherapy sometimes cause delayed effects,
leukocytes and platelets, hematuria, decreased
such as a second cancer that may appear years
body immune cells, hair loss in most patients,
later. The time taken to overcome some side effects
etc.
and regain the energy varies to each person and it
Cancer cells tend to grow fast, and chemo
depends on many factors, including health status
drugs kill fast-growing cells. However, since
and current medication.
these drugs spread throughout the body, they
can also affect the fast growing normal and
DISCUSSION
healthy cells. The damage to the healthy cells
Indonesia is now developing PGB-0, which is
causes side effects. Some chemo drugs cause
B-10 that mixed with curcuma analogue as cancer
long-term side effects, such as heart or nerve

3

treatment. Based on GLOBOGAN (IARC)
2012, breast cancer had the highest percentage
of new cases among all kind of cancers, which
was 43.3% with mortality rate by 12.9%. If the
cancer can be detected early it will lead to better
recovery process (Globogan, 2012). The
province of Yogyakarta had the highest cancer
prevalence of 4.1%o with estimated absolute
number of 14.596 people. Cervical and breast
cancer had the highest prevalence in Indonesia
in 2013, namely cervical cancer by 0.8%o and
breast cancer by 0.5%o, whereas the highest
prevalence of cervical cancer is 1.5%o and 2.4%
breast was in The Special Region of Yogyakarta
(Riskesdas, 2013).
The new concept of BNCT, which is a
radiation binary targeted for cancer treatment,
consists of a combination of two approaches
that have never been used in the previous
synergism. This combination brings a realistic
hope to patients with recurrence or metastatic
cancer. This therapy assumes that anti-HER2
monoclonal antibody boronas (MABs) is given
to patients and accumulated in tumor. Then the
tumor is destroyed when exposed to neutron
irradiation. Because the use of anti-HER2 MAB
shows good and promising results, the concept
of BNCT is expected to strengthen the
therapeutic effect. It can be the most likely
Figure 1. The Application of
PGB-0 in BNCT and co-
chemotherapy agent.
additional treatment for patients with severe breast
cancer, patient with metastatic cancer who is failed
to show improvement with other treatment method,
and patients who refuse the standard treatment
protocol.
The complexity of cancer causes many types of
proteins that play a role in the growth and
malignancy of cancer cells. One biomarker of
cancer that is widely used as a therapeutic target is
HER2. This compound has been proved to has the
ability to interact with cancer markers specifically
and has a significant effect in the treatment of
cancer. Pentagamabororonon-0 (PGB-0) is and
analogue of curcumin that has the same therapeutic
effect as curcumin which shows inhibition of
cancer cells that express HER2 protein (cellMCF-7
/ HER2). This curcumin analogue is still under
development in Indonesia. The combination of
PGB-0 and chemotherapy agent is known to inhibit
the migration of metastatic breast cancer cells. It is
hoped that PGB-0 will have two way of
developments, which are as a delivery agent 10-B
for BNCT and as a co-chemotherapy, as described
in Figure 1.
A potential increase in therapeutic ratio of
subcellular boron biodistribution is showed on
microdosimetry examination. The clinical case
studies of technique simulation show the
advantages of using BNCT for the treatment of
4
breast cancer with positive HER2. BNCT is a Radiat Isot 2011; 69(12): 1882-4. doi:
cell targeted therapy that kills only specific 10.1016/j. apradiso.2011.03.036.
cancer cell, so that it has relatively no adverse 6. American Cancer Society, 2016.
effects. Chemotherapy side effects. Retrieved from:
https://www.cancer.org/treatment/treatments-
CONCLUSION and-side-effects/treatment-
BNCT brings a new hope to cancer patients types/chemotherapy/chemotherapy-side-
in Indonesia, especially the breast cancer effects.html
patients. It is expected that with PGB-0, it will
be easier to carry out therapy with BNCT soon.
The cancer patients in Indonesia are waiting for
the beneficial cancer treatment, accurately
treating patients without leaving adverse effects.

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