JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
JOURNAL of NUCLEAR and Related TECHNOLOGIES
Vol. 12, No. 2, December 2015
(ISSN 1823-0180)
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
JOURNAL of NUCLEAR and Related TECHNOLOGIES (JNRT)
Vol. 12, No. 2, December 2015
CONTENTS
THE RELATIONSHIP BETWEEN INACTIVATION RATE OF V79 CELLS
AND PHYSICAL QUALITY PARAMETERS OF DEUTERON AND HELIUM
PARTICLES AT LOWER DOSES 1
Abubaker Ali Yousif, Ismail Bin Bahari, Muhamad Samudi Yasir
OVERVIEW OF INAA METHOD AND ITS APPLICATION IN MALAYSIA 11
A.R.Yavar, S. B. Sarmani, H. Khalafi, A. K. Wood, K. S. Khoo
EVALUATION OF TUMOUR CELLS DAMAGE FOLLOWING 30
RADIOTHERAPY BY TC-99M PERTECHNETATE
Muhammad Afiq Bin Khairil Anuar, Siti Zanariah Ab Aziz, Raizulnasuha Abdul Rashid , Safri
Zainal Abidin, Norhayati Dollah , Wan Nordiana A Abd Rahman
INTERCELLULAR UPTAKE OF TECHNETIUM-99M PERTECHNETATE 35
BY DIFFERENT TYPES OF CELL LINES
Safri Zainal Abidin, Raizulnasuha Abdul Rashid, Muhammad Afiq Khairil Anuar, Wan
Nordiana A Abd Rahman
A SURVEY ON THE USAGE AND DEMAND OF MEDICAL 40
RADIOISOTOPE & RADIOPHARMACEUTICALS IN MALAYSIA
Muhammad Fakhrurazi Ahmad Fadzil, Siti Selina Abdul Hamid, Siti Najila Mohd Janib,
Azahari Kasbollah, Syed Asraf Fahlawi Wafa
FICUS DELTOIDEA ENHANCE GLUCOSE UPTAKE ACTIVITY IN 56
CULTURED MUSCLE CELLS
Zainah Adam, Shafii Khamis, Amin Ismail and Muhajir Hamid
PURIFICATION AND CONCENTRATION OF GALLIUM-68 VIA ANION 68
EXCHANGE METHOD FROM A SNO2 -BASED COLUMN GERMANIUM-
68/ GALLIUM-68 GENERATOR
Muhammad Fakhrurazi Ahmad Fadzil, Mohd Khairul Najah, Ng Yen, Siti Najila Mohd Janib,
Noor Hasnah M. Khairullah
RADIATION DAMAGE IN THE SILICON DIOXIDE (SIO2) LAYER 83
Fuei Pien Chee, Haider F. Abdul Amir, Abu Hassan Husin, Saafie Salleh, Afishah Alias
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
NEUTRON SPECTROMETRY OF THERMAL COLUMN BY VARIOUS 90
FILTER/MODERATING MATERIALS AT REACTOR TRIGA PUSPATI FOR
BNCT RESEARCH
Mohd Rafi Mohd Solleh, Abdul Aziz Mohamed, Abd. Aziz Tajuddin, Faridah Idris, Megat
Harun Ar-Rashid, Mohamad Hairie Rabir, Muhammad Rawi Md Zin, Hafizal Yazid, Azraf
Azman
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
Nuclear Science Programme, School of Applied Physics, Faculti Science dan Technology, Universiti
Kebangsaan Malaysia, 43600 Bangi, Selangor Darul, Malaysia
e-mail: [email protected], Tel: +60172759427
ABSTRACT
To quantify the effectiveness of deuterons and helium particles at low doses, the inactivation rate in
vitro for V79 cells has been extracted from radiobiological published data. The Physical parameters
characteristics of these charged particles such as the linear energy transfer, the restricted linear
energy transfer, the linear primary ionization and the mean free path are determined. The
relationship between the inactivation rate and the physical parameters for deuterons and heluim-3
particles has been established in this research. This approach enables in getting the distinctive
biological response in terms of varies physical quality parameters. The best statistical regression
fittings are formulated for each correlation.
ABSTRAK
Untuk menentukan keberkesanan deuterons dan zarah helium pada dos yang rendah, kadar
inactivation dalam vitro untuk sel-sel V79 telah tercabut dari radiobiological data diterbitkan. Ciri-ciri
fizikal parameter ini zarah-zarah bercas seperti pemindahan tenaga linear, pemindahan tenaga linear
yang terhad, ionisasi utama linear dan laluan percuma min ditentukan. Hubungan antara kadar
inactivation dan parameter fizikal untuk deuterons dan zarah-zarah heluim-3 telah dibentuk dalam
kajian ini. Pendekatan ini membolehkan mendapatkan yang tersendiri berbeza-beza jawapan biologi
segi parameter fizikal kualiti. Kelengkapan statistik regresi yang terbaik akan digubal bagi setiap
korelasi.
Keywords: low dose, inactivation rate, physical parameters, deuterons, helium-3
INTRODUCTION
Absorbed dose as a fundamental physical parameter is utilized to quantify the amount of energy deposited by
charged particles in a critical volume in the matter. In radiation protection and radiation dosimetry, this
parameter is playing an important role as a universal physical quantity. Meanwhile in other fields such as
radiation biology, this distinctive quantity is applied to determine biological effects of ionizing radiations. The
relationship between the absorbed dose and the biological effect gives a suitable method to indicate the relation
between these two different parameters. Linear quadratic model is proposed to explain this relationship in
terms of the linear and quadratic coefficients which represent the radiation rates of producing cell killing by
primary single and double tracks charged particles. In this model the component is given as a linear function
of absorbed dose, while the component is given as a quadratic function of the absorbed dose.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
At lower doses, the inactivation rate in this model is usually applied to determine the probability of
occurrence of biological damage of ionizing radiation (Booz, & Feinendegen, 1988). Usually, this distinctive
component is defined as the inactivation rate of cell irradiated by ionizing radiations. The lethal effect
produced by single track per charged particle traversal the cell nucleus is given as the probability of energy
deposition events by charged particle in terms of (Alper, 1979). The average number of single hit leads to
inactivation of exposed cell is usually expressed in terms of .
Usually, alpha parameter depends on cell type and the charged particle that exposed to it, the physical quality
parameters which characterize the charged particles are crucial in determining the magnitudes of effectiveness
which related to the inactivation rate of irradiated cells. The relationship between the inactivation rate and
these radiation physical quality parameters such as energy, linear energy transfer, linear primary ionization,
mean free path and effective charge is not completely addressed for all charged particles especially deuterons
and heliums particles, which carry more weight in this research.
Identification of distinctive relationships between the inactivation rate and the physical quality parameters
will enable in understanding the underling biophysical mechanism of radiation action of low doses.
The relationship between and linear energy transfer LET is not well established. The optimum value of LET
usually occur 1994) but this typical value is not peculiar for all radiation types. This
statement means that the optimum value of LET for any quality of charged particle and for any biological end-
point is independent of radiation quality and the type of lethal damage of the exposed cells. As a part of this
work, the validity of this assumption will be tested statistically in terms of the best correlation of all
characterized physical quality parameters presented graphically against the inactivation rate . The
parameters involve are the particle energy E, the linear energy transfer LET, the linear primary ionization I,
the mean free path and the effective charge Zeff. Multiple regressions fitting of the best correlations will be
drawn out and the best correlations between the inactivation rate and the physical quality parameters are
modelled.
MATERIALS AND METHOD
The dependence of the inactivation rate of V79 cells irradiated in vitro by deuterons and helium particles
were characterized based on the physical quality parameters. The analysis was carried using secondary data
published by various researchers (Belli et al. 1994; Cherubini et al. 1994; Wouters, 1996). The inactivation rate
is mainly extracted from all sigmoid survival curves which are matched the following model (Horowitz, y.
2006):
S (D) eDD2 (1)
Where D is absorbed dose given in Gy, represents the inactivation rate and represents the quadratic rate of
inactivation, S(D) gives the ratio of survival fraction of V79 cells after irradiation.
1 (2)
D0
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
D0 corresponds to the average dose required to score an average one ionization event per cell. The particle
energy and LET are taken directly from each original experiment or interpolated utilizing the tabulated values
provided by (Watt, D. E. 1993) which determined using the following equations:
The linear primary ionization is given as follows: as follows
I (nm1 ) 0.01536 Z Z2 1 1 (3)
A eff IP Tmax
2
The radiation mean free path is determined as follows:
(nm) 1 (4)
I
Where the maximum delta-ray energy Tmax, and the ionization potential IP of water are in eV.
RESULTS AND DISSCUSSION
The relation between and energy E of deuterons is shown in Figure 1. There is a non-linear relationship
between these physical and biological parameters. At the beginning, the inactivation rate of V79 decreases
slightly with increasing deuterons energy reaches the minimum at 103 keV of deuterons energy, later the
inactivation rate levelled off as the energy increases, thereafter the inactivation rate declines sharply as the
energy of deuterons increases.
(Gy-1) 3.0
2H
2.5 Regr.
Conf.
2.0 Pred.
1.5
1.0
0.5
0.0
1e+3 2e+3 2e+3 3e+3 3e+3 4e+3 4e+3
E (keV)
Figure 1. The relationship between inactivation rate and energy E for deuterons. The
legends provided in the small box indicate particle type, regression line, confident
interval, and predicted relation.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
The best regression model of this relation is given as the following: numbering
equation (5)
(E) C1E C2E2 C3E3 C4 ,
where C1 6.55103 , C2 3.47106 , C3 5.961010 , C4 6.58 and r2= 1.
Figure 2 indicates the relationship between and energy E for helium particles. It is noted that there is an
inverse non-linear relation between these parameters. The inactivation rate decreased with the energy of helium
particles.
This relation can be demonstrated mathematically as follow: equation no. (6)
(E) C20E C21E 2 C22E3 C23 ,
where C20 1.59 103 , C21 1.68107 , C22 5.971012 , C23 5.86 and r2= 1.
0.95 3He
0.90 Regr.
0.85 Conf.
Pred.
(Gy-1) 0.80
r ²= 1
0.75
0.70
0.65
6000 7000 8000 9000 10000 11000 12000
E (keV)
Figure 2. The relationship between inactivation rate and energy for helium particles. The
legends provided in the small box indicate particle type, regression line, confident
interval, and predicted relation.
The relationship between Linear Energy Transfer LET for deuterons and inactivation rate is plotted in Figure
3. The inactivation rate increases gradually with LET and reached the maximum value of inactivation rate at
41 The predicted movement of LET against should be decreased. This well half bell-shape response
is not established before for this particle. This distinctive response can be presented mathematically as follow:
(LET ) C5LET C6LET 2 C7LET 3 C8 , equation no. (7)
where C5 0.16, C6 105103 , C7 1.55105 , C8 0.86 and r2= 1.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
Figure 4 indicates the relationship between the inactivation rate of V79 cells and the Linear Energy Transfer
LET of helium particles. As similar of Figure 3, the inactivation rate of V79 cells increases linearly with
increasing of energy deposition rate LET up to the maximum at 59 shape of correlation can be
modelled as follow: as follows:
(LET ) C24LET C25LET 2 C26 , equation no. (8)
where C24 8.41103 , C25 7.52105 , C26 0.14 and r2= 1.
2H
3.0 Regr.
Conf.
2.5 Pred.
2.0
(Gy-1) 1.5
1.0 r ²= 1
0.5
0.0
5 10 15 20 25 30 35 40 45
LET (keV/m)
Figure 3. The relationship between inactivation rate and linear energy transfer for
deuterons. The legends provided in the small box indicate particle type, regression
line, confident interval, and predicted relation.
0.95 3He
0.90 Regr.
0.85 Conf.
Pred.
(Gy-1)
0.80
0.75 r ²= 1
0.70
0.65
42 44 46 48 50 52 54 56 58 60
LET (keV/m)
Figure 4. The relationship between inactivation rate and linear energy transfer for helium
particles. The legends provided in the small box indicate particle type, regression
line, confident interval, and predicted relation.
The relation between inactivation rate and restricted Linear Energy Transfer for deuterons and helium-3
particles are represented in Figure 5 and Figure 6 respectively.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
3.0 2H
2.5 Regr.
2.0 Conf.
Pred.
(Gy-1) 1.5
r ²= 1
1.0
0.5
0.0 5 10 15 20 25
0
LET100 (keV/m)
Figure 5. The relationship between inactivation rate and restricted linear energy transfer for
deuterons. The legends provided in the small box indicate particle type, regression
line, confident interval, and predicted relation.
0.95 3He
0.90 Regr.
0.85 Conf.
Pred.
(Gy-1)
0.80
0.75 r ²= 1
0.70
0.65
22 24 26 28 30 32 34
LET100 (keV/m)
Figure 6. The relationship between inactivation rate and restricted linear energy transfer for
helium particles. The legends provided in the small box indicate particle type,
regression line, confident interval, and predicted relation.
For both particles, the inactivation rate increases dramatically as the restricted ionization density increases.
The maximum inactivation rates of deuterons and helium-3 particles occur at 23.14 32.26
respectively. These responses are also described mathematically as follow:
For deuterons, the model is given as follow: as follows
equation (9)
(LET100) C9LET100 C10LET1002 C11LET1003 C12 ,
where C9 0.30 , C10 5.68103 , C11 2.63105 , C12 0.85 and r2= 1.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
For helium-3, the model is given as follow: as follows
(LET100) C27LET100 C28LET1002 C29 , equation (10)
where C27 0.03 , C28 1.02 103 , C29 0.88 and r2= 1.
Figure 7 shows the relation between the inactivation rate and the linear primary ionization I for deuterons.
As the linear ionization increases, the inactivation rate increases as well. The maximum value of linear
ionization occurs at 0.24 nm-1.
10
2H
Regr.
Conf.
Pred.
(Gy-1) 1
r ²= 1
0.1 0.1 1
0.01
I (nm-1)
Figure 7. The relationship between inactivation rate and linear primary ionization for
deuterons. The legends provided in the small box indicate particle type, regression
line, confident interval, and predicted relation.
This relationship can be described mathematically as follow: as follows
equation (11)
(I ) C13I C14I 2 C15I 3 C16 ,
where C13 10.83 , C14 7.64 , C15 1.84 , C16 4.61 and r2= 1.
Relationship between inactivation rate and linear primary ionization I for helium-3 particles is shown in
Figure 8. The inactivation rate rises gradually with increasing linear ionization of helium-3 particles. The
maximum value of inactivation rate comes out at 0.9 Gy-1 when linear ionization is equal to 0.25 nm-1. The
mechanism of inactivation of V79 can be interpreted obviously in terms of this distinctive parameter. By
comparing the responses in Figure 7 with Figure 8, it can be noted that the deuterons are more capable in
producing the inactivation of V79 cells than helium-3 particles. In contrast, the helium-3 particles yield the
highest inactivation at lower energy deposition events.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
0.95 3He
0.90 Regr.
0.85 Conf.
Pred.
(Gy-1) 0.80
0.75
0.70
0.65
0.14 0.16 0.18 0.20 0.22 0.24 0.26
I (nm-1)
Figure 8. The relationship between inactivation rate and linear primary ionization for helium
particles. The legends provided in the small box indicate particle type, regression
line, confident interval, and predicted relation.
The best fitting model which describes this relationship is given as follow: as follows
equation (12)
(I ) C30I C31I 2 C32 ,
where C30 1.40 , C31 10.21, C32 0.64 and r2= 1.
Figure 9 illustrates the relationship between the inactivation rate of V79 cells and the mean free path for
deuterons. The inactivation rate starts decrease sharply as the mean free path increases holding the minimum,
later the inactivation rate increases as the mean free path increases. The relation can be fitted accurately
applying the following model:
() C17 C182 C19 , equation (13)
where C17 0.19 , C18 2.57 , C19 3.53 and r2= 1.
Finally, the relationship between inactivation rate of V79 cells and the mean free path for heluim-3 particles is
represented in Figure 10. At the beginning, the inactivation rate decrease rapidly as the mean free path
increases, subsequently the inactivation slightly decreases as the mean free path increases, beyond the
inactivation rate decreases dramatically as the mean free path of helium-3 particles rises. Mathematically this
relation is modelled according to the following expression: equation (14)
() C30 C312 C323 C33 ,
where C30 3.54 , C31 0.63, C32 0.04 , C33 7.43 and r2= 1.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
3.5 2H
3.0 Regr.
2.5 Conf.
2.0 Pred.
(Gy-1) 1.5 r ²= 0.9
1.0
0.5
0.0
-0.5 10 20 30 40 50
0
(nm)
Figure 9. The relationship between inactivation rate and mean free path for deuterons. The
legends provided in the small box indicate particle type, regression line, confident
interval, and predicted relation.
Representing inactivation rate of V79 cells in terms of the physical quality parameters which characterize both
deuterons and heluim-3 particles allows extensive investigation of the involved mechanism of inactinvathioins erfefegction
yielded by these charged particles at low doses where the radiation effects at this region is not absolutely
predictable in terms of the convention quantity the absorbed dose, that is often use as a universal measure
physical of biological effects of ionizing radiation at higher doses. used as a universal
physical
0.95 measurement of
3He
0.90 Regr.
Conf.
0.85 Pred.
(Gy-1) 0.80
0.75
0.70
0.65
4.0 4.5 5.0 5.5 6.0 6.5 7.0
(nm)
Figure 10. The relationship between inactivation rate and mean free path for helium
particles. The legends provided in the small box indicate particle type, regression
line, confident interval, and predicted relation
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
important to indentify the
CONCLUSSION governed the
It is very important for identifying the physical parameters which are ruled the mechanism of energy deposition
events in the medium. The absorbed dose as a universal physical parameter in determining the inactivation of
cells is not reliable especially at lower doses. The Investigation on the variation of the inactivation rate twoitrheveal
the proposed physical quality parameters has the potential in revealing the specific information on the cellular
and sub-cellular structural details of radiosensitive sites within the biological targets, the nature of the damage
mechanism involved and the suitability of the quality parameters for quantifying the occurred biological effects
(end-points).
should be AKNOLEDGGEMENT
in one
paragrap I sincerely acknowledge the school of applied physics for technical assistant and guidance in carrying out this
h research.
I would like also extend my sincere gratitude to the Libyan high education committee for the financial support
in bringing the research to a success.
I would also like to this opportunity to extend my thanks to all my colleagues and friends for their wonderful
advice and assistance.
REFERENCES
Booz, J. & Feinendegen, L. E. (1988). A microdosimetric understanding of low-dose radiation effects. Int. J.
Radiat. Biol. 53, 1, 13-21.
Alper, T. (1979). Cellular Radiobiology. Cambridge University Press.
Hall, J. E. (1994). Radiobiology for the Radiologist, J. B. Lippincott Company.
Belli, M., Cera, F., Cherubini, R. (1994). Inactivation induced by deuterons of various LET in V79 cells, Rad.
Prot. Dosim., 52, 1-4, 305-310.
Cherubini, R., Michael, & Goodhead, D. T. (1994). Molecular and cellular effectiveness of charged particles
(light and heavy ions) and neutrons. Progress Report, FI-CT920053, Sector: BI3.
Wouters, B. G., Lam, G. K. Y., Oelfke, U., Gardey, K. (1993). Measurements of relative biological effectiveness
of the 70 MeV-proton beam at TRIUMF using Chinese Hamaster V79 cells and the high precision cell
sorter Assay. Rad. Res., 146, 159-170.
Horowitz, y. (2006). Microdosimetric Response of Physical and Biological Systems to Low-and High-LET
Radiations: Theory and Applications to Dosimetry. Elsevier, British Library.
Watt, D. E. (1993).
100eV to 1GeV, University of St. Andrews, St. Andrews, fife KY16 9TS, Report biophysics/1/93.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
aSchool of Applied Physics, Faculty of Science and Technology, Universiti Kebangsaan Malaysia
(UKM), 43600 Bangi, Selangor, Malaysia.
bChemistry Programme, School of Chemical Sciences & Food Technology, Faculty Science and
Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor, Malaysia.
cNuclear Science and Technology Research Institute (NSTRI), Atomic energy organization of Iran,
North Kargar Avenue, P. O. Box: 14155-1339, 14374, Tehran, Iran.
dAnalytical Chemistry Application Group, Industrial Technology Division, Malaysian Nuclear Agency
(MNA), Bangi, 43000 Kajang, Selangor, Malaysia.
*e-mail: [email protected]
ABSTRACT
Present work shows the development of nuclear technology in Malaysia and highlights its applications
that have been developed by using the instrumental neutron activation analysis (INAA) method. In
addition, present study exhibits a comprehensive review of INAA for calculation of neutron flux
parameters and concentration of elements. The INAA is a powerful method to analyse the sample
which identifies qualitative and quantitative of elements present in a sample. The INAA is a working
instrument with advantages of experimental simplicity, high accuracy, excellent flexibility with respect
to irradiation and counting conditions, and suitability for computerization. In INAA, sample is
irradiated and measured directly. In practical, INAA is based on an absolute, relative and single-
comparator standardisation method. The INAA has been developed since 1982 when the
TRIGA Mark II reactor of Malaysia has commissioned. The absolute method was Malaysia
less utilised, the relative method has been used since 1982, and the k0-INAA method is
derived from single-comparator standardization method has been developed since 1996 in Malaysian.
The relative method, because of its advantages, such as high accuracy, easy for using, has the most
applications
in Malaysia. Currently, local Universities and Malaysian Nuclear Agency (MNA)
application
research reactor use INAA method in Malaysia. semasa menunjukkan semakan
yang komprehensif terhadap
universities
bersifat sederhana ABSTRAK penggunaan teknik INAA dalam
pengiraan parameter berkaitan
Kajian ini menunjukkan pembangunan teknologi nuklear di Malaysia danflumkesnynerelauhtkraonn ddeanngaknepekatan unsu
aplikasi yang telah dibangunkan dengan menggunakan kaedah analisis pengaktifan (INAA) memainkan
peranan penting neutron. Di samping itu, kajian hadir mempamerkan kajian semula komprehensif
INAA bagi pengiraan neutron sentiasa berubah-ubah parameter dan kepekatan unsur-unsur. INAA ini dalam
adalah satu kaedah yang berkuasa untuk menganalisis sampel yang mengenal pasti unsur-unsur yang
hadir dalam sampel kuantitatif dan kualitatif. INAA itu adalah satu instrumen bekerja dengan
kelebihan eksperimen kesederhanaan, berteknologi, fleksibiliti yang cemerlang berkaitan dengan
sinaran dan mengira keadaan dan kesesuaian untuk pengkomputeran. INAA, sampel adalah disinari
keadaan
pembilanga 11 sampel disinar
n
Dalam teknik INAA,
dan menggunakan
JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volutmeek1n2i,kNo. 2, December 2015.
Secara praktikal, perbandingan-satu
secara relatif
dan diukur secara langsung. Praktikal, INAA adalah berdasarkan satu kaedah penyeragaman mutlak, digunakan
relatif dan satu-comparator. INAA tersebut telah dibangunkan sejak tahun 1982 Bilakah reaktor
TRIGA Mark II Malaysia telah ditauliahkan. Kaedah yang mutlak adalah kurang digunakan, kaedah
relatif telah digunakan segerak. sejak
Keywords: Instrumental Neutron Activation Analysis (INAA), k0-INAA method, Absolute
method, Relamtiavenamkeathloadkaedah relatif digunakan sejak 1982, dengan kaedah k0 diterbitakan daripad
kaedah perbandingan-satu secara relatif. Keadah relatif ini, dengan kelebihannya sep
kejituan tinggi dan mudah digunakan, mempunyai paling banyak penggunaannya di
Malaysia. Pada masa ini, reaktor penyelidikan di Agensi Nuklear Malaysia dan univers
tempatan di Malaysia menggunakan teknik INAA.
INTRODUCTION
Neutron Activation Analysis (NAA) was introduced by Georg von Hevesy and Hilde Levi as a method for the
quantitative determination of element concentrations an early as 1936, in which neutrons are used to activate
nuclei in the sample. All atomic nuclei in the sample have a probability of capturing a neutron. This
probability is expressed in units of area and called the neutron capture cross section (σ). The neutron flux is
expressed as intensity per unit area per unit time (n/cm2/sec). Nuclei with the same number of protons but
different numbers of neutrons are isotopes of each other, i.e. belong to the same element. The fraction of nuclei
belong of a certain element that have a particular number of neutrons is the isotopic abundance (θ). After capturing a
s neutron, the nucleus may have become unstable, i.e. radioactive. The level of induced radioactivity depends on
deenetercgtyedoftaThhseteanebumlmeibtftoeerrdmo,γf -igrtaemnysearycaateenmdbiutenγdste-atrbeacleytesnd, uecwalceithihawnaidtshetmhaeipchoaanrltdfiucluicftleaoror fpdtrehotbeecartbaoidrliitowyniutchcalliladedev.etWrhyehheanibgshdoeleucntaeeyriggnaygmrametsaoaluilnatttioeennr s.tiitImnypwe(trhγhte)oea.steenltesmen
peaks resulting γ-ray spectrum, the energy of a detected peak indicates what element was present in the sample, and
indicates the area of the detected peak allows for the quantitative determination of amount of the element present in the
sample. The INAA with main advantages as compared to some other trace element analysis techniques are as:
INAA is non-destructive, i.e. the sample need not be dissolved and the probability of loss or contamination is
he areas untdheerrefore low; INAA is nuclear, i.e. the method is independent of the chemical and physical state of the sample;
he detectedINAA is insensitive to low-Z element, i.e. other elements in low-Z matrices can be determined with high
eaks allow sensitivities; INAA is linear, i.e. after calibration at only one concentration level, the technique is accurate no
absolute, relative or single-comparator standardization method [1-12].
In the beginning, the Ra-Be mixtures were used as neutron source. The long-lived radium (Ra-226) radioactive
isotope will decay by emitting an alpha particle and this particle is just like helium (He) nucleus with 2 protons
and 2 neutrons. When mix this source with a sample of light isotope such as beryllium (9Be) and the following
reaction will occur:
9 Be 4He12C 1n
Later, with the development of the nuclear reactor, a powerful neutron source has become more available,
yielding substantially larger neutron fluxes and therefore providing the feasibility of determination of lower
concentrations or the analysis of smaller samples. The Geiger-Muller (GM) counter was used for counting beta
and -rays. However, there was no energy resolution available. Therefore, all elements were identified based on
half-lives and chemical separations carried out after the irradiation. This technique is called radiochemical NAA
(RNAA). Later, with the development of NaI scintillation detectors introduced the possibility of measuring a -
ray spectrum with an energy resolution of 4 % at 1 MeV. Then, improvement was made when Ge(Li)
semiconductor material was applied for analysis with 0.1 % resolution at 1 MeV. The advantage of these
detectors is that the chemical separation steps are skipped. The INAA then was introduced.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
imprecisioThe application of the absolute neutron activation method goes back more than 50 years, that the first
ns shall systematic methodological investigation was reported by GIRARDI et al. during the time of scintillation
be detectors. In the absolute standardization method, the physical parameters determining an elemental
factored characteristic, e.g. σ, θ, γ and M (atomic mass) are taken from literature. For many (n, γ) reactions of interest,
in these parameters are not precisely known. Because they were determined by independent methods, their
imprecision will add up when calculating amounts of elements, leading to large systematic errors of more than
the 100% in some cases. The use of the absolute method presents several advantages over the relative method on small i
amount the basis of speed, cheapness, versatility and ease of automation. It also presents the possibility of multi- in It
element analysis in one single irradiation. But its disadvantages are as: It has been long recognized that the
nuclear data, γ-ray emission probabilities and neutron fluxes are the major sources of errors in the absolute
method. Indeed they are and they have to be known with reasonable precision. This method will work well in
very stable reactors where flux changes are negligible, otherwise continuous flux monitoring is essential. The
efficiency, essential coincidence and attenuation corrections and geometry may reduce the achievable precision
particularly when extended sources are to be counted [4, 5, 7, 9, 13].
The absolute method calculates the ρa concentration (g/g) of elements as:
a 1.6611024 Np M (1)
.S.D.C.t .R.
paragraph W c . p
which Np is measured gamma net peak area (counts); tc is counting time; S is saturation factor; S 1 eti ,
with ti irradiation time and ln 2 with T1/2 half life; D is decay factor; D etd , with td decay time; C is
T1/ 2
counting factor; C (1 etc ) / tc , correcting for decay during counting; W is mass of irradiated element
(g); θ is Isotope abundance (fraction); εp is Full-energy peak detection efficiency; and R is reaction rate.
Also the absolute method is utilised for calculation of thermal to fast neutron flux ratio (ffast) and fast neutron
flux (ϕfast) using the reaction of 58Fe(n, γ)59Fe 96Zr(n, γ)97Zr/97mNb as follows [4,
5, 7, 9, 13]:
new ASP,2 . . f . P,1 (2)
paragraph ASP,1 . M 1 Q0,2 ( ) P,2
f fast . . .
f
M 2
fast th (3)
f fast
where the specific count rate (s-1g-1) is defined:
ASP NP / tC (4)
SDCW
Q0 () is obtained as:
Q0 ( ) Q0 0.429 0.429 (5)
1).(0.55)
(2
Er
Er is effective resonance energy in eV; Q0 I0 0 with I0 is the resonance integral for the (n, γ) reaction and
σ0 is the thermal neutron cross section (2200 ms-1); M is atomic mass (g.mol-1); α is expression for the deviation
of the epithermal neutron distribution from 1/ E shape, approximated by a 1/ E1 dependence.
13
) should be (psi JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
epi)
The th is the thermal neutron flux (cm-2s-1); the thermal neutron flux ( th ) and epithermal neutron flux ( epi
) are calculated as follow:
th (f f Asp,Au 3.47 (6)
Q0,Au ( )) p,Au (7)
epi th
f
The absolute method is utilised in the fast neutron activation analysis (FNAA). The most important
applications of FNAA are the analysis of oxygen content in a wide variety of matrices including metals,
geologic materials, coal, liquid fuels, ceramic materials, petroleum derivatives and fractions and chemical
reaction products. The determination of nitrogen in biological materials, including nitrogen as a measure of
protein content as well as nitrogen determination in fertilizers, explosives, and polymers is also important
applications. Other elements that are routinely analyzed by FNAA include Ag, Al, Au, Si, P, F, Cu, Mg, Mn,
Fe, Zn, As, and Sn [4, 5, 7, 14-21].
In the relative standardization method, the unknown sample is irradiated together with a calibration sample
containing a known amount of the element of interest. The calibration sample or standard is measured under
the same conditions as the sample. The ratio of the net areas of the photo peaks corresponding to the element
of interest in the two measured spectra is used to calculate the concentration. Advantages of this method are
as: In this procedure, all parameters except the half life of the radionuclide of interest cancel out and therefore
are of no consequence. This standardization method is still being regarded as one of method which has the
highest accuracy of NAA. It eliminates many errors such as those due to flux parameters, nuclear data, decay
scheme, efficiency, self-shielding, coincidence summing. Disadvantages of this method are as: It is not suited for
multi-element analysis. It is impossible to put individual standard for all 70 detectable elements that might be
present in the sample in the same place as the sample during irradiation. It is also virtually impossible to
produce a multi- element standard containing known amounts of all these elements with sufficient accuracy,
homogeneity and stability. Sometimes, certified reference materials are used as multi-element standards. This is
a dangerous practice, because reference materials are not primary standards certified concentration often are
imprecise, sometimes even inaccurate.
The r concentration (g/g) of elements in sample is obtained by measurment of sample and comparator (*) as
follows:
W Np * (8)
.S.D.C.t P
r c
Np * P
.S.D.C.t
W c
In ideal case the ratios S*/S and ε*/ε are equal to unity [3, 7-9].
The single comparator standardization method makes multi-element analysis with INAA feasible. Assuming
stability in time of all relevant experimental conditions, standards for all elements are irradiated each in turn
with the chosen single comparator element. Once the sensitivity for all elements relative to the comparator
element is known, this comparator element can be used in routine measurements instead of separate standard
for each element.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
The original single comparator method is expressed in the definition of the k-factors, which are experimentally
determined by irradiation of a standard and a single-comparator:
small w in Where M c s s 0,s f Q0,s ( ) . p,s (9)
M s cc 0,c f Q0,c ( ) p,c
kc (s) .
Where, c and s denote for comparator and standard elements, respectively. These k-factors, obtained from
direct measurements, are usually much more precise than independent physical parameters obtained from
literature data in the absolute standardization method. On the other hand, the measured k-factors are valid
only for a specific detector, counting geometry and irradiation facility, and remain valid only as long as the
neutron flux parameters of the irradiation facility remain stable. The standardization methods have usefully
contributed in many application fields of NAA, however, they have also been prompted by the inconveniences
in application, i.e. in the relative standardization, the experimental workload, the impossibility to quantify
unexpected elements and the unsuitable for multi-element analysis; in the absolute standardization, the
inaccuracy and inconsistency of the nuclear data; and in the single-comparator standardization, the inflexibility
with respect to varying irradiation and counting conditions. The advantages of this method are as: Although it
presents similar advantages to that of absolute methods, the problem of flux variations is removed when using
the comparator method. Moreover, the flux-ratio, efficiency, k0, etc. may be determined precisely hence
reducing contributions to the total uncertainty. The disadvantages of this method are as: The problem of
choosing suitable comparator elements for multi-element analysis may not be easy as far as nuclear data and
decay scheme parameters are concerned. In the every day practice of NAA, counting at small source-to-detector
distances for extended sources is common, problems of correction for coincidences and attenuation may involve
tedious calibration procedure, experimental corrections and a complicated computer calculation [1-7, 9-11].
(i) should be in the
next line
-
Through the years, many efforts have been spent to overcome the disadvantages of the above mentioned
standardization methods. Generally, the required aspects for a new standardization protocol are: (i)
experimental simplicity; (ii) high accuracy; (iii) excellent flexibility (with respect to the irradiation and counting
conditions); and (iv) suitability for computerization. That is the reason so that the k0-standardizaTtihoen smeetahroed the
for INAA (k0-INAA), one of the remarkable developments of INAA launched in the mid-70s. It is rneoat saotnhseory
comma , describing a physical phenomenon, but a protocol for calibration procedures. It has been developed as an
missing absolute standardization where the unreliable nuclear data are replaced by accurate experimentally determined
compound nuclear constants, so called k0-factors, or as a single-comparator standardization which is made
small flexible with respect to varying characteristics of the k0-factors, the independence with irradiation and
w in measurement conditions is done, k0-factor is expressed: expressed as
Whic (10)
h k0,c (s) M c ss 0,s
M s cc 0,c
Which can be tabulated and published in literature as a generally useful parameter. Then, by converting
k0,m (s) k0,c (s) / k0,c (m) , the irradiated sample with monitor m, the analytic concentration can be obtained
[22]. The k0-method was formulated in the Høgdahl convention and Westcott-formalism. The parameters such
α) are determined by
the Høgdahl convention. Since the applicability of Høgdahl convention is restricted to (n, γ) reactions for which
Westcott s g- -1/ν (n, γ) reactions of nuclides
(e.g, 176Lu, 151 ≠1. For the k0-NAA to be generally applicable for all nuclides, the
Westcott-formalism is adopted and parameters such as the modified spectral index r( ) Tn T0 , the
Westcott gLu (Tn ) factor and the absolute neutron temperature Tn are determined besides α and [1-11, 23-
34].
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
The α factor
The α factor can be determined from three method: Cd-ratio, Cd-coverd, and bare
irradiation methods as described below [1, 9, 11, 35-37]:
-covered multi-
A set of N monitors is irradiated simultaneously under Cd-covered and subsequently counted
on a Ge-detector, α can be obtained as the slope -α of the straight line when plotting:
log (E r,i ) ( Asp,i )Cd versus log E r,i (11)
ko,Au (i). p,i .FCd,i .Qo,i ( ).Ge,i
Cd is Cd-transmission factor and Ge is epithermal Neutron
Self-shielding Correction. The left hand term of Eq. (11) is itself a function of α, and thus an
iterative procedure should be applied. aslo α can be solved as follows:
N N
N log E r,i
i1
log E r,i logTi
logTi
i1 i1 (12)
N N
0
N
small w
N log E r,i
log E r,i i1
i1 N
With
Ti (E r,i ) ( Asp,i )Cd (13)
ko,Au (i). p,i .FCd,i .Qo,i ( ).Ge,i
When a irradiation of Au and Zr monitors is made under Cd-cover, i.e. in Eqs. (11), (12) & (13), N=3 and a
-covered multi- --
new method.
paragraph
-ratio for multi-
A set of N monitors is irradiated with and without Cd-cover, and the induced activities are measured on a Ge
detector. The α can be obtained as the slope -α of the straight line when plotting:
small w log (E r,i ) versus log E r,i (14)
(FCd,i .RCd,i 1).Qo,i ( ).Ge,i / Gth,i
th is correction factor for thermal neutron self-
shielding.
-covered multi- α can be solved from Eq. (12) with:
(15)
Ti (E r,i )
(FCd,i .RCd,i 1).Qo,i ( ).Ge,i / Gth,i
In this method, the use of monitors with very high Q0-value should be avoided.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
-
-cover, thereafter
the induced activities are measured on a Ge-detector. In this method, there is a possibility to make use of the
(a b)Q0,1( )Ge,1 / Gth,1 aQ0,2 ( )Ge,2 / Gth,2 bQ0,3 ( )Ge,3 / Gth,3 0 (16)
With (17)
a 1 Asp,2 . k0,Au (1) . p,1 1 ;b 1 Asp,3 . k0, Au (1) . p,1 1 96Zr(n, γ)97Zr/97m
Asp,1 k0,Au (2) p,2 Asp,1 k0, Au (3) p,3
which it come with irradiation Au and Zr monitors under
94Zr(n, γ)95Zr; 197Au(n, γ)198Au.
-
, -
-isotopic -ratio method using Eq. (18) as follows [1, 9, 11, 35-37]:
f (FCd RCd 1)GeQ0 () / Gth (18)
In Eq. (18), the monitor used is an element which is irradiated subsequently with and without Cd-cover. A gold
or cobalt monitor is suitable for this requirement. It is obviously that the α-value must be inputted to calculate
the Q0 () parameter.
A proven technique for in- - -
96Zr(n, γ)97Zr/97m 94Zr(n, γ)95Zr.
Ge,1 k0,Au (1) . p,1 .Q0,1 ( ) Ge,2 Asp ,1 .Q0,2 ( ) (19)
k0,Au (2) p,2 Asp ,2
f Asp ,1
Gth , 2 Asp , 2 k0,Au (1)
Gth ,1 k0,Au (2) . p ,1
p,2
- -determination.
-
The S0,Lu ( ) factor
The value of S0,Lu ( ) determine using the following expression:
S0 ( ) S0 (1eV ) (20)
Er
Where S0 is the corresponding quantity for an ideal 1/E epithermal neutron flux distribution [3, 7, 9].
r( ) Tn T0
The modified spectral index r( ) Tn T0 is a measure for the epithermal to total neutron density ratio. It
-
isotopic 96Zr(n, γ)97Zr/97m 94Zr(n, γ)95Zr:
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with paragraph, not
indented
Gth,2 . k0,Au (1) p ,1 .g1 (Tn ) Gth ,1 . ASP,1 .g 2 (Tn ) (21)
k0,Au (2) . p,2 ASP,2
r( ) Tn
T0
Gr,2 . ASP,1 .S 0, 2 ( ) Gr ,1 . k0,Au (1) p ,1 .S0,1 ( )
ASP,2 k0,Au (2) . p,2
where Gr is correction factor for resonance neutron self-shielding and gLu (Tn ) is the Westcott g-factor at
a neutron temperature Tn . Also r( ) Tn T0 can be obtained from the "Cd-ratio" method:
r( ) Tn Gth .g(Tn ) (22)
T0
RCd .FCd g(Tn ).(1eV ) 2 W ( ) Gr .S0 ( )
K.(1 2 ).ECd Gr .S0 ( )
which W ( ) W .(Er ) (1eV )
The W' is known value for each nuclide. K 1 ECd with E0 0.0253 eV[3, 7, 9].
4 E0
gLu (Tn )
The gLu (Tn ) factor and Tn ν Lu target (reaction of
176Lu(n, γ)177Lu) and pure 1/ν 96Zr(n, γ)97Zr/97mNb;
94Zr(n, γ)95 197Au(n, γ)198Au) by following express:
k ASP g1/ v (Tn ) r( ) Tn T0 s0,Lu ( ) (23)
0, Au .
g Lu (Tn ) P Lu Tn T0 s0,1/ v ( ) r( )
P
k ASP
0, Au . 1/ v
The corresponding r( ) Tn T0 values use to calculate the gLu (Tn ) factor. The Tn value obtains using the
literature values of gLu (Tn ) vs. Tn [3, 38].
should be in line
with paragraph, not
ndented, smThaellcwoncentration of an element in a sample by Høgdahl convention is calculated as:
n Where N P / tC
SDCW a
H . 1 . Gth,m . f Ge,m .Q0,m ( ) . p,m (24)
ASP,m k0,m (a) Gth,a . f Ge,a .Q0,a ( ) p,a
Where H is concentration of analyst a (in g/g); m is irradiated neutron fluence rate monitor and W is
sample mass (in grams). The actual equation used in the Westcott formalism for W concentration (in
g/g) calculation is:
N P / tC 1 g Au (Tn ) r( ) Tn S 0,Au ( ) p,m (25)
SDCW a T0
W
ASP,m k0,m (a) g a (Tn ) r( ) Tn p,a
T0 S 0,a ( )
The Eq. 25 is utilised for concentration calculation of the Westcott elements such as 176Lu(n, γ)177Lu, 151Eu(n,
γ)152Eu, 151Eu(n, γ)152mEu, 153Eu(n, γ)154Eu, 164Dy(n, γ)165mDy, 164Dy(n, γ)165Dy, 168Yb(n, γ)169 and 175Lu(n, γ)176mLu
[3, 5, 7, 9].
18
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delete
The TRIGA Mark II reactor of the Malaysian Nuclear Agency (MNA) was commissioned in 1982. This reactor
uses light-water as moderator, coolant and reflector. The fuel assembly consists of an alloy of uranium enriched
to 20% U-235 and zirconium hydride (U-ZrH). Several experimental facilities are available in the MNA research
reactor. For activation analysis and isotope production, a rotary specimen rack is located around the top
portion of the core and inside the reflector. The rotary specimen rack assembly consists of ring-shaped, seal-
welded aluminium housing containing an aluminium rack mounted on special bearings. The rotary rack (RR)
fonts supports 40 evenly spaced tubular aluminium containers that serve as receptacles for the specimen containers.
not
standa Each receptacle has an inside diameter of 3.17 cm and height of 27.4 cm and can hold two specimen containers.
rdize
At Present most of reactor operation time has been utilised for samples irradiation related to
the INAA application. Majority of the samples are from MNA analytical chemistry
laboratory, and the rest of the samples are from local universities [39]. forty
As shown in Fig 1. only one study by absolute method [40], Forty five studies by relative method [41-85], and
nineteen studies by k0-INAA [86-104] were carried out in Malaysia. It indicates the relative method, because of
its advantages as easy for using, had the most application in Malaysia.
As shown in Fig. 2, most of application of INAA in Malaysia is in environmental field (29 papers), 17 papers in
nutritional epidemiological studies, 7 papers in nuclear data studies, 4 papers in quality assurance of analysis
and reference materials studies, 3 papers in industrial materials analysis, 3 papers in geology and geochemistry
studies, 2 papers in archaeological studies, and 0 paper in forensic studies [40-104].
In order to utilising of INAA method as entirely, determination of parameters f , , f fast , th , epi , fast ,
S0 () , r( ) Tn T0 , gLu (Tn ) and Tn are necessary. The parameters of f and α determined for first time
α are useful for trace elements by k0-INAA method base on
Høgdahl convention. The parameters of th and epi calculated by Wee et al. [98] for first time in Malaysia.
The th and epi evaluate distribution of neutron flux in reactor. The parameters of f fast and fast determined
by Yavar et al. [101] for first time in Malaysia. The parameters of f fast and fast are useful for FNAA
applications. In order to using the FNAA, special facilities need to install in MNA research reactor. The
parameters of S0 () , r( ) Tn T0 , gLu (Tn ) and Tn were determined by Yavar et al. [104] for first time in
Malaysia. The Westcott parameters of S0 () , r( ) Tn T0 , gLu (Tn ) and Tn use to trace elements that
-1/ν (n, γ) reactions of nuclides (e.g, 176Lu, 151 ≠1.
Figure 1. Number of publications related to absolute, relative and k0-NAA methods in
Malaysia since 1982.
19
JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
Figure 2. Number of publications related to INAA applications in Malaysia
CONCLUSION
The INAA method has utilised as a powerful instrument for determination of elemental concentration in
Malaysia since 1982. The INAA was developed as absolute, relative and k0-INAA methods, respectively. The
INAA utilises to trace elements present in geological, environmental, and biological samples. The absolute
method is useful for FNAA application. After installation of FNAA facilities in Malaysian Nuclear Agency
(MNA) research reactor, FNAA applications will be used in Malaysia. The k0-INAA method based on Høgdahl
convention and Westcott-formalism has developed for determination of neutron flux parameters at MNA
research reactor and trace elements increasly since 1996 in Malaysia. The relative method by advantage of
experimental simplicity has the most application in Malaysia.
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and other parametric methods of INAA in Cuba. Part I. Journal of Radioanal. Nucl.
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Calculated from the Neutron Spectrum and k0 and Q0 Values. Journal of Radioanal.
Nucl. Chem. 245(1): 167-172.
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reactor for k0-NAA and application to medium-lived nuclides. Journal of Radioanal. and
Nucl. Chem. 257: 525-529.
Akaho E.H.K, & Nyarko B.J.B (2002) Characterization of neutron flux spectra in irradiation
sites of MNSR reactor using the Westcott-formalism for the k0 neutron activation
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Nuclear Instruments and Methods in Physics Research Section A: Accelerators,
Spectrometers, Detectors and Associated Equipment. 556: 386-390.
Alghem H.L, & Ramdhane M (2008) Characterization of neutron spectrum at Es-Salam
Research Reactor using Høgdahl convention and Westcott formalism for the k0-based
neutron activation analysis. Journal of Radioanal. and Nucl. Chem. 278(3): 627-630.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
Embarch K, Bounakhla M, Bajja A, Ibnmajah M, Jacimovic R, Smodis B, Byrne A, & Sabir
A (2004) Instrumental neutron activation analysis of Moroccan geological samples using
the k0-standardization method. Journal of Radioanal. Nucl. Chem. 261: 43-49.
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Nigeria Research Reactor-1 (NIRR-1) for the k0-NAA standardization. Journal of
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Moon J.H, Kim S.H (2007) Application of the k0-NAA method at the HANARO research
reactor. Journal of Radioanal. Nucl. Chem. 271(2): 289-295.
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standardization at PINSTECH. Radioanal. and Nucl. Chem. 277: 525-529.
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accuracy and precision of the experimental α-determination in the 1/E1+α epithermal
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TRIGA Mark II Reactor Facility, Malaysian Nuclear Agency research reactor, Bangi,
Malaysia.
Ibrahim N, Fen L.H & Wood A.K (2009) Absolute method quantitative identification of
elements by NAA using reactor Triga PUSPATI. J. Sains. Nukl. Malays. 21(1): 49-56.
Arshad M.Y (1982) Determination of copper and molybdenum in human fingernails and hair
by neutron activation analysis. Ph.D Thesis. University Kebangsaan Malaysia, Bangi,
Selangor.
Bobaker A.M (2005) Development and application of extraction techniques for the
determination of manganese in water by neutron activation analysis. Ph.D Thesis.
University Kebangsaan Malaysia, Bangi, Selangor.
Elakeili I (2004) Determination of total mercury and methylmercury in scalp hair samples of
Kuala Lumpur residents by neutron activation analysis. Ph.D Thesis. University
Kebangsaan Malaysia, Bangi, Selangor.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
Elias B.S, Wood A.K, Sulaiman Z.A, Alzahrany A.A, Elias M.S. & Wee B.S (2007)
Determination of heavy metal pollution in depth profile of marine sediment samples
from the Strait of Malacca. PSP, Fresenius Environmental Bulletin. 16(10): 1279-1287.
Hamzah A. & Sarmani S.B (1987) A water quality survey of the langat River, Selangor,
Malaysia. Malays. Applied Biol. 16: 369-377.
Hamzah A, Sarmani S, Liow J.Y. & Abugassa I (2004) Studies on elemental analysis of
chinese traditional herbs by neutron activation technique and their mutagenic effect. J.
Radioanal. Nucl. Chem. 259 (3): 499-503.
Hamzah M.S, Rahman S.A, Wood A.k, Elias M.S, & Salim N.A (2009) Characterization clay
bricks from structures of historical sites using neutron activation analysis and statistical
methods. J. Sains. Nukl. Malays. 21(1): 41-48.
Majid A, Sarmani S.B, & Yusoff N.I (1995) Trace elements in Malaysia medicinal plants. J.
Radioanal. Nucl. Chem. 195: 173-183.
Rahman S.A, Hamzah M.S, Wood A.K, Elias M.S, & Zakaria K (2008) INAA of ancient
glass beads from Sungai Mas archaeological site, Bujang Valley, Malaysia. J. Radioanal.
Nucl. Chem. 278(2): 271-276.
Rahman S.A, Wood A.K, Sarmani S.B, & Majid A.A (1997) Determination of mercury and
organic mercury content in Malaysian seafood. J. Radioanal. Nucl. Chem. 217: 53-56.
Ramli A.T, Wahab M.A, & Wood A.K (2009) Environmental 238U and232Th concentration
measurements in an area of high level natural background radiation at Palong, Johor,
Malaysia. J. Of Environmental Redioactivity. 80. 3; 287-304.
Sarmani S.B (1987) A study of trace element concentrations in human hair of some local
population in Malaysia. J. Radioanal. Nucl. Chem. 110: 627-632.
Sarmani S.B (1989) The determination of heavy metals in water, suspended materials and
sediments from Langat River, Malaysia. Hydrobiol. 176/177: 233-238.
Sarmani S.B, Wood A.K, Hamzah Z, & Majid A.A (1993) Analysis of toxic trace elements in
sea food samples by neutron activation. J. Radioanal. Nucl. Chem. 169(1): 255-258.
Sarmani S.B, Kiprawi A.Z, & Ismail R.B (1994) Mercury determination in hair of Malaysia
fishermen by neutron activation analysis. Biol. Trace Element Res. 43/45: 435-441.
Sarmani S.B, Abdullah M.P, Hamzah A, & Rahman A (1996) Analysis of methylmercury in
biological samples by gas chromatography and neutron activation. Proc. 5th Edrasia
Conf. Chemical Sciences. Guangzhou.
Sarmani S.B, Hassan R.B, Abdullah M.P, & Hamzah A (1997) Determination of mercury
and methylmerccury in hair sampls by neutron activation. J. Radioanal. Nucl. Chem.
216: 25-27.
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Sarmani S.B, Abdullah M.P, & Bobaker M.A (2004) Preconcentration of trace manganese
from natural waters by complexation with dithiocarbamate and adsorption onto C18-solid
phase extraction column for nuetron activation analysis. J. Radioanal. Nucl. Chem.
259(2): 257-260.
Sarmani S.B, & Alakili I (2004) Determination of total mercury and methymercury in hair
samples from residents of Kuala Lumpur, Malaysia by neutron activation analysis. J.
Radioanal. Nucl. Chem. 259(2): 261-264.
Sarmani S.B, & Bobaker A.M (2005) Monitoring and evaluation of the concentration levels
of manganese species in the raw and finished waters of three water treatment plants in
the Linggi river basin, Malaysia. Poll. Res. 24(3): 1-5.
Sarmani S.B, & Alakili I (2004) Application of neutron activation analysis for mercury
species determination in scalp hair samples from Malaysia, Libya and Jordan. J.
Radioanal. Nucl. Chem. 262(1): 41-48.
Shamsiah A, Sarmani R.S, Majid A, & Wood A.K (1995) The determination of mercury and
methylmercury in seafood by neutron activation analysis. Malays. J. Anal. Sci. 1: 221-
228.
Sharma A.K, Sarmani S.B, & Tjell J.C (2004) Arsenic concentration in hair as an indicator
of exposure. Malays. J. Sciences 23: 227-234.
Yusof M.R, Wood A.K, & Shafil A.F (1987) Multielemental Analysis of an Industrial Source
Emission by Neutron Activation Analysis, A Case Study of A Palm-oil Mill Plant.
Seminar on the application of nuclear techniques in industry, Kuala Lumpur.
Yusof A.M, Akyil S, & Wood A.K (2000) The Assessment of Marine Sediment Pollution
From Rare Earth Elements (REE) Distribution Pattern Using Instrumental Neutron
Activation Analysis (INAA). Malays.J.Anal.Sci. 2: 19-29.
Yusof A.M, Thanapalasingham A.K.V, Akyil S, & Wood A.K (2005) The Assessment of a
River Ecosystem Health Due to the Impact of Pollution From Industrial Discharge
Using INAA and ICP-MS. Ist. Int. Nuclear Chemistry Congress (1st. INCC).
Yusof A.M, Chia C.H, & Wood A.K (2005) The Speciation of Cr(III) and Cr(VI) in Surface
Waters With a Chelex-100 Resin Column and Their Quantitative Determination Using
ICP-MS and NA INCC).
Yusof A.M, Akyil S, & Wood A.K (1999) The Assessment of Marine Sediment Pollution
From Rare Earth Elements (REE) Distribution Pattern Using Instrumental Neutron
Activation Analysis (INAA). paper presented at Simposium Kimia Analisis Malaysia ke-
12, UPM, Terengganu.
Yusof A.M, Rahman N.A, & Wood A.K (1993) The Use of Neutron Activation Analysis in
Trace Elements Study in Marine Samples. proceedings of the International Chemical
Conference on Materials Science and Environmental Chemistry of Main Group
Elements, Kuala Lumpur.
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Yusof A.M, Misni M, & Wood A.K (1997) Determination of Inorganic Selenium Species by
Neutron Activation Analysis in Aquatic Species after Preconcentration with Ammonium
Pyrrolidinecarbodithioate. J. Radioanal. Nucl. Chem, 216(1): 59-63.
Yusof A.M, Hanafiah Z, & Wood A.K (1998) Speciation of Se(IV) in Marine Sediments
Using Neutron Activation Analysis After Co-precipitation With
Dibenzyldithiocarbamate (DBDTC) With Phenolphtalein. The Science of Total
Environment, 214, 247-252.
Yusof A.M, Ting S.W, Wang L.K, & Akyil S (2001) Determination of Natural Radioactivity
in Public Drinking Water Quality Assessment. J.Radioanal.Nucl.Chem, 249(1): 233-238.
Yusof A.M, Akyil S, & Wood A.K (2001) Distribution of Rare Earth Elements in Sediments
of a Polluted Marine Environment by Instrumental Neutron Activation Analysis. J.
Radioanal. Nucl. Chem, 249(2): 333-341.
Yusof A.M, Rahman M.M, & Wood A.K (2004) Neutron Activation Analysis in the
Speciation of Some Trace Elements in Water Samples After Pre-concentration on
Activated Carbon. J. Radioanal. Nucl. Chem. 259(3): 479-484.
Yusof A.M, & Wood A.K (1990) Environmental Assessment of Sediments Along The Coastal
Areas of South Johore, Malaysia Through Elemental Analysis. paper sent for
presentation at The 7th. Symposium On Radiation Measurements and Applications, The
University of Michigan, USA.
Yusof A.M, Rahman N.A, & Wood A.K (1993) The Use of Neutron Activation Analysis in
Trace Elements Study in Marine Samples. paper presented at The International
Chemical Conference on Material Science and Environmental Chemistry of Main Group
Elements, Kuala Lumpur.
Yusof A.M, Rahman N.A, & Wood A.K (1994) The Use of Trace Element Analytical
Techniques in Marine Environmental Risk Assessment Study. paper presented at The
ASEAN-Canada Cooperative Programme on Marine Science Mid-Term Technical
Review Conference, Singapore.
Yusof A.M, Misni M, & Wood A.K (1995) Determination of Inorganic Selenium Species by
Neutron Activation Analysis in Aquatic Species after Preconcentration with Ammonium
Pyrrolidinecarbodithioate. paper presented at The 9th. International conference on
Modern Trends in Activation Anayisis (MTAA-9), Seoul, Korea.
Yusof A.M, Hanafiah Z, & Wood A.K (1997) Speciation of Se(IV) in Marine Sediments
Using Neutron Activation Analysis After Co-Precipitation With
Dibenzyldithiocarbamate (DBDTC) With Phenolphtalein. The 4th. International
Conference on Trace Metals in Aquatic Environment, Kuala Lumpur.
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Yusof A.M, Akyil S, & Wood A.K (2000) Distribution of Rare Earth Elements in Sediments
of a Polluted Marine Environment by Instrumental Neutron Activation Analysis.
5th.International Conference of Methods and Applications of Radioanalytical Chemistry
(MARC-V), Kona, Hawaii, U.S.A.
Yusof A.M, Gill S.K, Salleh S, Akyil S, Hamzah S, Rahman S.A, & Wood A.K (2000) The
Use of Neutron Activation Analysis in Environmental Pollution Studies. The 2000
Workshop on the Utilization of Research Reactors, Taejon, Korea.
Yusof A.M, Rahman N.A, & Wood A.K (2002) Neutron Activation Analysis in the
Speciation of Some Trace Elements in Water Samples After Pre-concentration on
Activated Carbon. Int.Symp. Nuclear Analytical Methods in the Life Sciences, Antalya,
Turkey.
Yusof A.M, Rahman N.A, & Wood A.K (2004) Studies on the Adsorption Capacity of Some
Toxic Elements in Water Samples on Modified Activated Carbon, Activated Carbon and
Red Soil Using Neutron Activation Analysis. 11th. Int. Conf. on Modern Trends in
Activation Analysis (MTAA-11), Guildford, United Kingdom.
Yusof A.M, Thanapalasingham V, & Wood A.K (2005) The Assessment of a River
Ecosystem Health Due to the Impact of Pollution From Industrial Discharge Using
INAA and ICP-MS. Ist. Int. Nuclear Chemistry Congress (1st. INCC), Kusadasi,
Turkey.
Zahrany A.A (2007) Elemental distributions in marine sediments in the Straits of melaka
using neutron activation and Mass spectroscopic analyses. Ph.D Thesis. Universiti Putra
Malaysia.
Abugassa I, Sarmani S, & Samat S (1996) Development of k0-standardization method for
reactor neutron activation analysis. Sains Malaysiana 25(3): 47 54.
Abugassa I (1999) A study of instrumental neutron activation analysis based on k0-
standardization method developed for environmental materials. Ph.D Thesis. University
Kebangsaan Malaysia, Bangi, Selangor.
Abugassa I, Sarmani S, & Samat S.B (1999) Multielement analysis of human hair and
kidney stones by instrumental neutron activation analysis with the k0-standardization
method. Appl. Rad. Iso. 50 (6): 989-994.
Abugassa I, Sarmani S, & El-Ghawi U (2004) Instrumental neutron activation analysis based
on k0-standardization method as compared with other methods in the analysis of the
IAEA inter-comparison test. J. Radioanal. Nuclear Chem. 259(3): 381-384.
Embarch K, Bounakhla M, Bajja A, Ibnmajah M, Jacimovic R, Smodis B, Byrne A, & Sabir
A (2004) Instrumental neutron activation analysis of Moroccan geological samples using
the k0-standardization method. Journal of Radioanal. Nucl. Chem. 261: 43-49.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
Khoo K.S (2006) Multielement analysis for environmental impact assessment of solid wastes
generated by incineration plants. Ph.D Thesis. University Kebangsaan Malaysia, Bangi,
Selangor.
Khoo K.S, Sarmani S, & Abugassa I (2007) Determination of thermal to epithermal neutron
flux ratio (f), epithermal neutron flux shape factor (α) and comparator factor (Fc) in the
Triga Mark II reactor, Malaysia. Radioanal. Nucl. Chem. 271: 419-424.
Rezaee K, Elias S.B, Wood A.K, & Abdi M (2009) Rare earth elements distribution in
marine sediments of Malaysia coasts. J. Rare Earths. 27(6): 1066-1071.
Rezaee K, Elias S.B, Wood A.K, & Abdi M (2010) Rare earth elements determination and
distribution patterns in surface marine sediments of the South China Sea by INAA,
Malaysia. J. Radioanal. Nucl. Chem. 283(3): 823-829.
Sarmani S.B, Abugassa I, & Hamzah A (1998) Instrumental neutron activation analysis of
environmental samples using the k0-standardization method. J. Radioanal. Nucl. Chem.
234: 17-20.
Sarmani S.B, Abugassa I, Hamzah A, & Yahya M.D (1999) Elemental analysis of herbal
preparations for traditional medicine by neutron activation analysis with the k0-
standardization method. Biol. Trace. Element Res. 71-72: 365-376.
Shafaei M, Saion E, Wood K, Halimah M, Rezaee K, & Mehdipure L (2010) Evolution of 40K
in fruit collected in Malaysia by the determination of total potassium using neutron
activation analysis. Journal of Radioanal. and Nucl. Chem, 284(3), 659-662.
Wee B.S, Dung H.M, Wood A.K, Salim N.A, & Elias M.S (2006) Testing the applicability of
the k0-NAA method at the MINT's TRIGA MARK II reactor. Nuclear Instruments and
Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and
Associated Equipment. 564: 716-720.
Wee B.S, Wood A.K, Suhaimi H, Rahman S.A, Elias M.S, & Salim N.A (2007) Certified
reference materials for analytical quality control in neutron activation analysis. Malays.
J. Anal. Sci. 11(1): 17-22.
Wee B.S, Wood A.K, Hamzah M.S, Rahman S.A, Elias M.S, & Salim N.A (2007) Certified
Reference Materials For Analytical Quality Control In Neutron Activation Analysis. The
Malaysian J. of Anal. Sci. 11(1): 17 22.
Yavar A.R., Sarmani S.B., Wood A.K., Fadzil S.M., Radir. M.H. & Khoo K.S. 2011. Determination of fast
neutron flux distribution in irradiation sites of the Malaysian Nuclear Agency reactor. Applied Radiation
and Isotopes Journal. 69(5): 762-767.
Fadzil S.M, Sarmani S.B, Majid A.A, Khoo K.S, & Hamzah A. (2011) k0-INAA
measurement of levels of toxic elements in oil sludge and their leachability. Journal of
Radioanal. and Nucl. Chem, 287:41-47.
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Yavar AR, Sarmani SB, Wood AK, Fadzil SM, Masood Z, Khoo KS (2011) Neutron flux
parameters for k0-NAA method at the Malaysian Nuclear Agency research reactor after
core reconfiguration. Radiation Measurements Journal 46(2): 219-223.
Yavar, A.R., Sarmani, S.B., Wood, A.K. & Khoo, K.S. Development and implementation of
Hogdahl-Westcott method for the k0-INAA at Malaysian Nuclear Agency reactor.
Conference of Modern Trends in Activation Analysis-13, Texas A&M University, USA.
March 13-18, 2011.
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1 Medical Radiation Programme, School of Health Sciences, Universiti Sains Malaysia, Health
Campus, 16150 Kubang Kerian, Kelantan, Malaysia.
Corresponding author: Dr Wan Nordiana W Abd Rahman ([email protected])
ABSTRACT
Radiotherapy has become the most important modality in treating cancer with approximately 50% of
cancer patient undergo the treatment. However, more improvement to the radiotherapy treatment
efficacy is required to deprive cancer. Assessment of tumor progress during treatment is important to
accommodate the changes that occur during the fractionation course. The objective of this study is to
assess tumor cell damage after external beam radiotherapy by using technetium-99m
pertechnetate (99mTcO4-) as a tracer. In this study, HeLa cells were irradiated with 6 MV photon beam
with different radiation dose ranging from 0.5 Gy to 10 Gy. The irradiated cells were recultured in 6-
well plates and incubated for 10 days. After that, 2 mCi of 99mTcO4- were prescribed to each cell
colonies. The viable cells were separated from the rest and measured for 99mTcO4- uptake using single
head gamma camera with LEHR collimation. As results, the cells survival fractions clearly indicate
diminishing effect to the cells at higher dose of irradiation. Good correlation were observed between
99mTcO4 uptake and survival fraction for cells irradiated at lower dose and less significant correlation
were indicated at higher dose. In conclusion, there is potential for the efficacy of external beam
radiotherapy in treating cancer to be assessed by using radioisotope as a non-invasive tracer. In this
case, technetium-99m pertechnetate (99mTcO4) could be attached to the specific antibody so that better
correlation between the cells uptake and possible cell damages could be observed.
ABSTRAK
Radioterapi telah menjadi modaliti utama dalam merawat kaser, di mana lebih 50% pesakit kanser
melalui kaedah rawatan ini. Namun yang demikian, masih banyak ruang penambahbaikan perlu dibuat
untuk meningkatkan keberkesanan radioterapi dalam merawat kanser. Penilaian terhadap perubahan
tumor adalah penting ketika membuat sebarang perubahan sepanjang prosedur rawatan berlangsung.
Objektif kajian ini adalah untuk menilai kerosakan terhadap sel kanser akibat radioterapi dengan
menggunakan technetium-99m pertechnetate (99mTcO4-) sebagai penanda. Sel HeLa telah didedahkan
dengan pancaran foton 6 MV, yang mempunyai dos radiasi antara 0.5 hingga 10 Gy. Sel HeLa
tersebut kemudiannya dikultur semula dan diinkubasi selama 10 hari. Seterusnya sebanyak 2 mCi
99mTcO4- telah dimasukkan kedalam setiap bekas sel. Sel yang hidup diasingkan untuk diukur
kandungan 99mTcO4- menggunakan kamera gamma berkolimasi LEHR. Hasil kajian jelas menunjukkan
bahawa pecahan survival sel berkurangan apabila dos radiasi meningkat. Kolerasi antara survival sel
dan penyerapan 99mTcO4- adalah baik bagi dos rendah, namun kolerasi tersebut menurun apabila dos
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
meningkat. Konlusinya, radioisotop mempunyai potensi untuk digunakan sebagai penanda bagi melihat
keberkesanan radioterapi secara tidak invasif. Dalam kes ini, technetium-99m pertechnetate (99mTcO4-)
boleh disambung dengan antibody yang spesifik bagi meningkatkan kolerasi antara penyerapan 99mTcO4-
ke dalam sel dan kerosakan sel akibat radioterapi.
Keywords: technetium-99m pertechnetate, molecular imaging, radiotherapy
INTRODUCTION
Cancers have become a main prominent cause of deaths among men and women around the world. According
to GLOBOCAN (2012), an estimated 14.1 million new cancer cases and 8.2 million cancer-related deaths
happened in 2012, compared with 12.7 million of cases and 7.6 million of death in 2008. Prevalence assessments
for 2012 revealed that there were 32.6 million people (over the age of 15 years) alive who had a cancer
diagnosed in the previous five years (WHO, 2014).
Debate continues about the best treatment to handle malignancy. Although recombination of treatment
becomes most popular option to handle cancer, external beam radiotherapy is still a vital choice, especially if
the tumour is spreading within small sizes. The patient undergoes radiotherapy require post therapy assessment
-rays, Computed Tomography (CT) and Magnetic Resonance
Imaging (MRI) are commonly used for this purpose. But these modalities could assess response only after
patient had completed the all fractions of treatments because anatomical changed may occur only after
treatment. Efficacy of external beam radiotherapy could not be displayed with these diagnostic techniques
during early of treatment.
If the radiotherapy efficacy can be assessed earlier by assessing the tumour cells damage via molecular imaging,
treatment modification can be done and will possibly increase in the patient survival rate. The molecular
marker such as cell death can potentially be used to predict tumour cell damage and its relationship with
radiopharmaceutical uptake could be an indicator. Cell death was an essential biological processed for
eliminating abundant and unwanted cells during embryonic development, growth, differentiation and
maintenance of tissue homeostasis. There are few types of cell death, such as apoptosis, necrosis and mitotic
(Verheij, 2008). Studies suggested that apoptosis is a major form of cell death following radiotherapy (Yang et
al., 2012). To date, Annexin V-based tracers are the most frequently used agents for in vitro detection and
quantification of apoptotic cells (Khoda et al., 2012). However, more applicable technique is required to assess
tumour cell death in vivo and using nuclear medicine technique seems a good option.
The purpose of this study is to assess tumor cell damage after external beam therapy by using technetium-99m
pertechnetate (99mTcO4-) as a tracer. Correlation between irradiation dose and 99mTcO4- uptake by HeLa cells
were investigated.
MATERIALS AND METHODS
HeLa (ATCC® CCL-
Media, which was supplemented with 10% FBS and a 100 unit/mL penicillin-streptomycin. All cells were
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
incubated at 37oC and 5% CO2 humidified atmosphere. The cells were grown until confluence and harvested
using 0.25% Trypsin-EDTA.
Solid water phantoms were organized with the thickness 13.5 cm on LINAC table couch. Cells samples were
placed at the center of the beam on top of the solid water phantoms and then covered with 1.5 cm bolus. The
samples were irradiated with different radiation dose (0.5 Gy to 10 Gy) using 6 MV photon beam at 100 cm
SSD and 10 cm x 10 cm field size. The cell samples were counted immediately to see the viability right after
irradiation and then recultured for 10 days for the cells to form colony (clonogenic assay). After 10 days,
99mTcO4- uptake study was conducted on cell colony and the uptake were compared with the cells colony
formed.
The viability of irradiated cell samples was measured using tryphan blue exclusion methods. The cells were
stained using tryphan blue and counted on hemacytometer under microscope. The numbers of viable cells were
counted. The counting of viable cells versus non-viable cells were made possible by using trypan as the non-
viable cell cytoplasm will look darker compared to viable cell, which have clear cytoplasm after treated with
this assay (Strober, 2001).
Cell samples that have been incubated for 10 days were rinsed off of their cell media using 0.5 ml of PBS. Cells
were fixed using 0.5 ml ice cold methanol for 15 minutes. Crystal violet were used to stain the cells and after
staining process for 30 minutes, the cells were rinsed gently using tap water, then let to dry completely. The
visible cell colonies were counted using microscope and analyzed in form of cell survival fraction data using
OriginPro 7.5 software.
-
0.2 mCi of 99mTcO4- in form of sodium pertechnetate were administered into each samples. The samples were
incubated again for another 30 minutes to allow 99mTcO4- uptake by cells. After 30 minutes, the cells were
rinsed with 0.5 ml PBS. The cells were then make into suspension using Trypsin EDTA and were centrifuges at
1500 rpm for 5 minutes. The centrifuged cells were scanned using using gamma camera equipped with LEHR
collimator. 99mTcO4- uptake measurements were performed with the detector of gamma camera at 10 cm distance
to the cell samples. The count reading was measured for 100 second using 20% window at 140 keV. The
percentage 99mTcO4- uptake was calculated and graph 99mTcO4- percentage uptake versus irradiation dose was
plotted.
RESULTS AND DISCUSSIONS
In this work, HeLa cells were used as an in-vitro model to identify tumor cell damage after radiotherapy.
Figure 1 show the number of viable cells which were counted immediately after irradiation with different dose
of 6 MV photon beam. Figure 1 clearly shows that the number of viable cells correlates inversely with radiation
dose. The loss of reproductive capacity after radiation was associated with early cell death, which may
represent the effectiveness of radiotherapy techniques used in the treatment. Joiner and Kogel (2009) pointed
that the potential reason of the early cell death was resulting from activation of pathways in response to the
initial cellular damaged caused by irradiation (Joiner et al., 2009).
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Figure 1. The viable cells (cell/ml) measured immediately after versus
radiation dose (Gy)
Figure 2. Correlation between percentage 99mTcO4- uptake and survival
fraction of the HeLa cells.
The cell damage also has been assessed using colony forming assay. The cells that form colony were tested for
99mTcO4- uptake which was employed as indicator to assess cell damage in response to the radiation dose. Based
on Figure 2, the cell survival fraction clearly shows decrement as the radiation dose increases. However, 99mTcO-
- uptake among the irradiated HeLa cells does not show any significant correlation with survival fraction. This
4
result contradicted with another similar study conducted by Tabar et al. (2011) and Liang et al. (2008), which
used radiopharmaceuticals in evaluating chemotherapy efficacy. Both of these studies shows inverse relation
t is worth to point out
that their study used the radiopharmaceuticals that are already tagged with carriers that can selectively be
absorbed by their respective cell samples. So we assume that the reason for our contradicting results with these
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
studies is because of unsuitable pairing between radiopharmaceutical and target cells. Each
radiopharmaceuticals have their own affinity with different type of cells and tissues. 99mTcO4- are already well
known to be used clinically for thyroid imaging, parathyroid
suitable pairing of radiopharmaceutical and targeted cells is crucial. In this case, 99mTcO4- uptake by cells could
be optimized with specific antibody and targeting agent.
CONCLUSION
In conclusion, there is potential for the efficacy of external beam radiotherapy in treating cancer to be assessed
by using radioisotope as a non-invasive tracer. In this case, technetium-99m pertechnetate (99mTcO4) could be
attached to the specific antibody so that better correlation between the cells uptake and possible cell damages
could be observed. Further improvised study are advised so that we can understand more about the relation
between cell damages due to radiotherapy, and its effect on intercellular uptake of radiopharmaceuticals.
REFERENCES
International Agency for Research on Cancer. (2013) Latest world cancer statistics Global cancer burden rises
to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed. World Health
Organization. Http://www.iarc.fr., 28th April 2014.
Verheij, M. 2008. Clinical biomarkers and imaging for radiotherapy-induced cell death. Cancer and Metastasis
Reviews, 27, 471-480.
Yang, T., Haimovitz-Friedman, A. & Verheij, M. 2012. Anticancer therapy and apoptosis imaging. Exp Oncol,
34, 269-276.
Khoda, M., Utsunomiya, K., Ha-Kawa, S., Kanno, S., Kono, Y. & Sawada, S. (2012). An Investigation of the
Early of Radiation Induced Apoptosis by 99mTc-Annexin V ans 201Thallium-Chloride in a Lung Cancer
Cell Line.J. Radiat. Res., 53, 361-367.
Strober, W. (2001). Trypan Blue Exclusion Test of Cell Viability. Current Protocol in Immunology. 21:A.3B.1
A.3B.2. DOI: 10.1002/0471142735.ima03bs21.
Joiner, M. & Kogel, A.V.D. (2009). Basic Clinical Radiobiology. Hodder Arnold. Great Britain.
Tabar, E.B., Lambrecht, F.Y., Gunduz, C., & Yucebas, M. (2011). I Vitro Evaluation of Apoptosis Detection
by 99mTc-Tetrofosmin in MCF-7 Breast Cancer Cell Line. J Radional Nucl Chem 288:839-844.
Liang, J., Chen, Y., Huang, Z., Zhao, Y., & He, L. (2008). Early Chemotherapy Response Evaluation in
Tumour by 99mTc-DTPA-DG. Cancer Biother Radiopharm 23:363-370.
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-
1 Medical Radiation Programme, School of Health Sciences, Universiti Sains Malaysia, Health
Campus, 16150 Kubang Kerian, Kelantan, Malaysia.
Email: [email protected]
ABSTRACT
The purpose of this study is to determine the technetium-99m pertechnetate (99mTcO4) intercellular
uptake by different types of cell lines. HeLa, human fetal osteoblast (hFOB), glial and glioma cell lines
grown in 6-wells culture plates were incubated with 99mTcO4 of activity of 200, 400, 600, 800 and 1000
µCi for 30 minutes at 37oC and 5% CO2 humidified atmosphere. After incubation, the cells were
washed 3 times with phosphate buffer saline to remove the extracellular traces of 99mTcO4.
Measurements of the intercellular 99mTcO4 radioactivity were performed using single head gamma
camera and the percentage uptake of the 99mTcO4 into the cells was calculated. The intercellular uptake
of 99mTcO4 was found to be inversely correlate to the radioactivity. HeLa cell shows the highest uptake
followed by hFOB, glial and glioma cell lines. Comparison of uptake between normal and cancer cells
present indistinguishable results. The findings of this study suggest that the intercellular uptake of
99mTcO4 is highly dependent on the type of cells despite no significant different of uptake was found
between normal and cancer cell lines. The level of radioactivity is also an important determinant
factor that influence the uptake of 99mTcO4 into the cells. This study will be the first precedent toward
understanding the cellular characteristic and pharmacokinetic of non-invasive imaging tracer for
future molecular imaging and therapy.
ABSTRAK
Kajian ini bertujuan untuk mengenal pasti kadar penyerapan intersel technetium-99m pertechnetate
(99mTcO4) oleh jenis sel yang berbeza. Kumpulan sel HeLa, sel human fetal osteoblast (hFOB), sel glial
dan sel glioma dikultur dalam piring kultur dan diinkubasi bersama 200, 400, 600, 800 and 1000 µCi
99mTcO4 selama 30 minit (37oC, kelembapan atmosfera CO2 5%). Selepas proses inkubasi, sel dibasuh
dengan phosphate buffer saline untuk membuang sisa-sisa ekstrasel 99mTcO4. Pengukuran radioaktiviti
99mTcO4 intersel dilakukan menggunakan kamera gamma, kemudian peratusan serapan 99mTcO4 oleh
sel-sel dikira. Hasil kajian menunjukkan kadar serapan intersel 99mTcO4 berkadar songsang dengan
radioaktiviti. Sel HeLa menunjukkan kadar serapan yang lebih tinggi berbanding sel hFOB, diikuti
dengan sel glial dan sel glioma. Didapati tiada perbezaan kadar serapan antara sel kanser dan sel
sihat. Konklusinya kajian ini menunjukkan bahawa kemungkinan kadar serapan intersel terhadap
99mTcO4 sangat bergantung kepada jenis sel, namun tiada perbezaan signifikan ditunjukkan apabila sel
sihat dan sel kanser dibandingkan. Paras radioaktif juga merupakan factor yang penting dalam
mempengaruhi serapan 99mTcO4 oleh sel.
Keywords: Technetium-99m-pertechnetate, In-vitro, molecular imaging
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
INTRODUCTION
Cancer detection through variety of medical imaging procedures such as scanning using magnetic resonance
imaging (MRI), computed tomography (CT) scanner, single photon emission computed tomography (SPECT)
and positron emission tomography (PET) provide different information and details on the degree of malignancy
[1]. Screening cancer by employing radionuclide and appropriate radiotracer to identify diseases not only detect
the location of the disease but also the physiology of the abnormality that can significantly impact the cancer
patient management [2]. The details of the diseases at cellular level are vital for the accurate diagnosis and
treatment prescription [3]. Radionuclides such as technetium-99m-pertechnetate (99mTcO4) has been used as a
probes to understand the biological characteristic of the cancer cells by visualization, characterization and
quantification of pathophysiological processes at the cellular and subcellular levels [4]. The interaction between
cells and radiopharmaceutical, allows non-invasive detection and imaging of the cell growth and proliferation
throughout the body which has long been recognised to be of significant value in the diagnosis and staging of
cancer [5]. In this study, we determined the intercellular uptake of 99mTcO4 by different types of cell lines and
compare the uptake of different activity level and time of incubation. We also sought the correlation between
the cell uptake and cell viability of the normal and cancerous type of cells.
MATERIALS AND METHODS
.
All general chemical reagents and tissue culture reagents were purchased from Gibco, Life Technologies (USA) .
The radionuclide 99mTc, was obtained from a molybdenum-99-technetium-99m (99Mo-99mTc) generator located in
the Nuclear Medicine, Oncology and Radiotherapy Department, School of Medicine, Universiti Sains Malaysia.
The generator ELUMATIC III was purchased from the CIS Bio International (France). The Symbia-E gamma
camera (Siemens Medical Solutions, Illinois, USA) was used to measure the count of 99mTcO4 uptake by cells.
The experiments were conducted using four types of cell lines: glial cells (SVG p12), glioma (DTBRG-05MG),
) while HeLa cells were grown in Roswell Park Memorial Institute (RPMI)
1640 culture media with 10% Fetal Bovine Serum (FBS), 100 units/ml penicillin and 100 µg /ml streptomycin.
All cells were incubated at 37oC and 5% CO2 humidified atmosphere. The cells were grown in 75 ml flask until
confluence and were harvested for experiments using trypsin-EDTA. The trypsinized cells were plated in 6 well
plates and were incubated for 24 hours before the experiments.
.
The 99mTcO4 were prepared from 99Mo/99mTc generator, ELUMATIC III which produced an elution of a clear
and colourless solution of sodium pertechnetate. The volume of the eluted 99mTcO4 solution was around 5 ml
with radioactivity of 200, 400, 600, 800 and 1000 µCi. The activity was measured and verified using a dose
calibrator.
.
The cells were incubated with 99mTcO4 of different activities at 30 minutes, 1 hour and 1.5 hours of incubation
time. After incubation, the culture media were removed and the radioactivity in the culture media were
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
counted using a dose calibrator. The cells were then washed three times with phosphate buffer saline (PBS) to
remove the remaining 99mTcO4 on the cell monolayers. Cells were detached from the culture plate by adding 0.5
ml of trypsin-EDTA and then cell were re-suspended in fresh media. The cell suspension were then centrifuge
at 15,000 RPM for 5 minutes. The 99mTcO4 uptake by the cells was measured using gamma camera and the
result was expressed as the counts per minute (CPM). After the uptake measurement, the cell viability assay
using trypan blue exclusion method were performed to determine the percentage of cell viability. The
experiment was performed twice to confirm the reproducibility of the result.
RESULTS AND DISCUSSIONS
The data illustrated in figure 1 shows that, the maximum uptake by hFOB cell occurs at the 1.5 hours of
incubation. There are no differences of uptake between 0.5 hours to the 1 hours. Highest percentage uptake
were observed at the lowest activity of 99mTcO4 and percentage uptake were decreasing with increasing activity.
The data in the figure 2 shows the similar trend in 99mTcO4 cellular uptake by glial and glioma with the hFOB
cell line. The intercellular uptake for this both types of cells are relatively maximum at the lowest activity and
decreased with increasing activity of 99mTcO4. The glial recorded the higher percentage uptake at 9.44 ± 0.09 %
than the glioma cell line with 7.44 ± 2.12% percentage uptake at 200µCi activity. However, the percentage
uptake at higher activity show no significant differences. The figure 3 summarise the percentage uptake of all
four cells lines at different activity of 99mTcO4. The HeLa cell line shows the highest percentage uptake, 11.21 ±
0.69%, while the lowest uptake was observed at 7.44 ± 2.12% for glioma. This is followed by hFOB and glial
with percentage uptake of 10.02 ± 1.41% and 9.42 ± 0.09%, respectively. Correlation between intercellular
percentage uptake and cell viability are presented in figure 4. High cell viability increase the intercellular
uptake of the 99mTcO4 and when the viability is low, its lead to the low intercellular uptake of 99mTcO4.
Figure 1: Intercellular percentage Figure 2: Intercellular percentage
uptake at different uptake of 99mTcO4 by Glial
99mTcO4 incubation time and Glioma.
for hFOB cell line.
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Figure 3: Intercellular uptake of 99mTcO4 for different types of cell lines. The blurr lagends
measurement were performed after 30 minutes incubation at 37oC and
humidified with 5% CO2.
Figure 4: Intercellular hFOB and HeLa uptake in correlation with cell viability. The
decreased viability of cell lines will affect the uptake percentage of both
cancer and normal cell lines.
The results indicate that the intercellular uptake were maximum at lowest activity for all type of cells and
longer incubation time have no significant effects. Optimal cell incubation time were found to be around 30
minutes and longer incubation time may affect the radiation counts as a results to the short half-life of 99mTcO4.
The intercellular uptake of 99mTcO4 by different type of cells linked to the characteristic of the cells such as
metabolic activity, cellular function and doubling time. Cancer cell such as HeLa is rapidly dividing type of
cells were observed to have more uptake of 99mTcO4 compare to slow dividing cell such as hFOB. However,
comparison between normal and cancerous brain cells shows no significant difference in the uptake probably
linked to other factor such as drug resistant characteristic and physiological parameters such as plasma
membrane potential and intracellular pH [6, 7, 8].
CONCLUSION
The findings of this study suggest that the intercellular uptake of 99mTcO4 is highly dependent on the type of
cells despite no significant different of uptake was found between normal and cancer cell lines. The level of
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
radioactivity is also an important factor that influences the uptake of 99mTcO4 into the cells. The results also
shows correlation between the cellular uptake and the cell viability. Further studies need to be conducted to
confirm the relationship between radiotracer uptake and the cellular characteristics of the cells.
REFERENCES
Orazio Schillaci, Luca Filippi, Carlo Manni, and Riccardo Santoni (2007). Single-Photon Emission Computed
Tomography/Computed Tomography in Brain Tumors.
Society of Nuclear Medicine and Molecular Imaging (2012) What are Nuclear Medicine and Molecular Imaging.
Access from http://www.molecularimagingcenter.org/index.cfm?PageID=6362 on January 2014.
Michael A. De Miranda, A. Mark Doggett, Jane T. Evans (2005). Medical Technology: Contexts and Content
in Science and Technology Education.
Sanjiv Sam Gambhir (2007). Just what is molecular imaging. Society of Nuclear Medicine and Molecular
Imaging.
Fatma J. Al-Saeedi1, Princy M. Mathew, Yunus A. Luqmani (2013) Assessment of Tracer 99mTc(V)-DMSA
Uptake as a Measure of Tumor Cell Proliferation In Vitro.
N. Perek, D. Denoyer, F. Dubois and F. Koumanov (2002). Malignant Gliomas Display Altered Plasma
Membrane Potential and pH Regulation-Interaction with Tc-99m-MIBI and Tc-99m-Tetrofosmin Uptakes.
Matthews CME, Mallard JR (1965). Distribution of 99mTcO4 and tumour/brain concentrations in rats.
Mc. Afee, Fueger CF and Stern HS (1964). 99mTcO4 pertechnetate for brain scanning.
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
Medical Technology Division, Malaysian Nuclear Agency, Bangi 43000 Kajang, Selangor
ABSTRACT
Medical radioisotope is a small quantity of radioactive substance used in safe, cost effective, for the
purpose of diagnostic and therapy of various diseases. In Malaysia, the emerging of new nuclear
medicine centers or institutions in both government and private sectors rose abruptly for the past few
years. Currently, there are no data available on the usage and demand of medial radioisotope or
radiopharmaceuticals. Understanding the usage trending and demand of radiopharmaceuticals and
medical radioisotope is essential when related to technology changes in order to meet the market size
of these radiopharmaceuticals. Survey result found out that the highest demand and the highest usage
among all radioisotopes are Technetium-99m and Radioiodine isotopes such as the Iodine-131, Iodine-
131 MIBG, Iodine-123 and Iodine-123 MIBG. Currently, most of the medical isotopes and
radiopharmaceuticals are currently imported. Technetium-99m is the backbone of nuclear medicine
whereby more than 80% of Nuclear Medicine services utilize this radioisotope. Technetium-99m supply
chain is unstable globally and in coming future, two main reactors (Canada & Holland) that produces
60% of world Molybdenum-99 will shut down the operation and supply of Molybdenum-99 will be
disrupted. As for radioiodine services, currently, Iodine-
neighboring countries due to its short half-life. Iodine-123 is useful in diagnostic of thyroid related
diseases. As for PET services, the highest demands are F-18 FDG and Gallium-68 Generator for the
moment. However the survey data still did not include most of the PET centers in the Klang Valley,
northern area (Penang) and the new upcoming PET center in Southern Region (Malacca and Johor).
It is important for Malaysia to self-produced medical radioisotope and radiopharmaceuticals to meet
the market and local demand of these medical isotopes.
ABSTRAK
Radioisotop perubatan adalah kuantiti kecil bahan radioaktif yang digunakan dalam keadaan selamat
dan kos efektif, bagi tujuan diagnostik dan terapi pelbagai penyakit. Di Malaysia, penubuhan pusat-
pusat perubatan nuklear baru atau institusi di kedua-dua sektor kerajaan dan swasta meningkat secara
mendadak pada tahun-tahun kebelakangan ini. Pada masa ini, tiada data tersedia bagi mengetahui
penggunaan dan permintaan radioisotop atau radiofarmaseutikal. Memahami trend penggunaan dan
permintaan radiofarmaseutikal dan radioisotop perubatan adalah penting apabila berkaitan dengan
perubahan teknologi untuk memenuhi saiz pasaran radiofarmaseutikal ini. Hasil kajian mendapati
bahawa permintaan yang paling tinggi dan penggunaan yang tertinggi di kalangan semua radioisotop
adalah isotop Technetium-99m dan radioiodin seperti Iodin-131, Iodin-131 MIBG, Iodin-123 dan
Iodin-123 MIBG. Pada masa ini, sebahagian besar daripada isotop perubatan dan radiofarmaseutikal
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
diimport daripada luar negara. Technetium-99m merupakan tulang belakang kepada perubatan nuklear
di mana lebih daripada 80% daripada perkhidmatan Perubatan Nuklear menggunakan radioisotop ini.
Rantaian bekalan Technetium-99m adalah tidak stabil di peringkat global dan pada masa akan datang,
dua reaktor utama (Kanada & Holland) yang menghasilkan 60% daripada dunia Molybdenum-99 akan
menutup operasi dan pembekalan Molybdenum-99 akan terganggu. Bagi perkhidmatan radioiodin, pada
masa ini, Iodin-123 tidak boleh diperolehi di Malaysia dan negara-negara jiran disebabkan separuh
hayatnya yang pendek. Iodin-123 adalah berguna dalam diagnosis penyakit berkaitan tiroid. Bagi
perkhidmatan PET, permintaan tertinggi adalah F-18 FDG dan Gallium-68 Generator buat masa ini.
Walau bagaimanapun data kaji selidik itu masih tidak termasuk kebanyakan PET pusat di Lembah
Klang, kawasan utara (Pulau Pinang) dan pusat PET akan datang baru di Wilayah Selatan (Melaka
dan Johor). Adalah penting bagi Malaysia untuk menghasilkan sendiri radioisotop perubatan dan
radiofarmaseutikal untuk memenuhi permintaan pasaran tempatan.
Keywords: Radioisotope, Radio-pharmacy, PET, Isotope generator
INTRODUCTION
Radioisotopes and radiopharmaceuticals play an important role in nuclear medicine, where they are used
routinely in the clinics for the non-invasive diagnosis and treatment of various diseases, including some of the
most important and frequent ones, like cancers and cardiovascular diseases (R.J. Kowalsky and S.W. Falen,
2013). According to International Atomic Energy Agency (IAEA) database, currently, over 10 000 hospitals
worldwide use radioisotopes in medicine. Currently more than 80% of the medical radioisotopes are produced
by research reactors. The remaining isotopes are made by particle accelerators, mostly with cyclotrons and
sometimes with linear accelerators or by other methods (Kahn and Laura H, 2008). These isotopes can be used
in 2 forms: as sealed sources or as unsealed sources. Sealed sources are used essentially for the localised
treatment of cancers, like prostate or breast cancer. This is called brachytherapy. Unsealed radio-isotopes are a
crucial component of the radiopharmaceuticals that are widely used in a Nuclear Medicine field.
The emerging of new nuclear medicine centers or institutions in both government and private sectors rose
abruptly for the past few years in Malaysia. Currently, there are no data available on the usage and demand of
medial radioisotope or radiopharmaceuticals. Understanding the usage trending and demand of
radiopharmaceuticals and medical radioisotope is essential when related to technology changes in order to meet
the market size of these radiopharmaceuticals. The future technology changes in nuclear medicine are related
with the demand and the readiness of the healthcare professionals. Besides that, it also limited to the
availability of the imaging modalities, such as the gamma camera, SPECT-CT and PET-CT. Thus it is
important to provide a data on the trending usage and demand of these medical radioisotope and
radiopharmaceuticals in both private and government institutions within Malaysia.
MATERIALS AND METHOD
The study was conducted in centers or institutions that utilize Gamma Camera /SPECT/ PET CT or utilizes
any medical radioisotopes in both government and private sector. A survey for a period of 3 months (between
14th February 15th May 2015) was conducted across Malaysia. The questionnaire used in this study had
been developed with all the expertise from the Medical Technology Division of Malaysian Nuclear Agency. The
survey was distributed among healthcare professionals that involved working with medical radioisotope and
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JOURNAL Of NUCLEAR And Related TECHNOLOGIES, Volume 12, No. 2, December 2015.
radiopharmaceuticals in private, government and university based hospitals or institutions and was distributed
manually either by hand, mail or e-mail.
Inclusion criteria for the potential respondents are:
Healthcare professionals working in Nuclear Medicine Department
Healthcare professionals working in any Imaging Department involve with the usage of PET/CT,
SPECT/CT and Gamma Camera
Healthcare professionals dealing with therapeutic isotope
Healthcare professionals dealing with diagnostic isotope (both PET and SPECT isotope)
Healthcare professionals that have the authority in making clinical decision
The questionnaire was divided into five (5) main part which include the profile of the respondents, the usage
and demand of radioisotopes in General Nuclear Medicine Services, the usage and demand of radioisotopes in
PET Nuclear Medicine Services, the usage and demand of isotopes in Radioiodine Services and the usage and
demand of radioisotopes used in Therapeutic Radiopharmaceuticals. The values were expressed as actual
numbers and corresponding percentages. Data is presented in either pie chart or bar chart.
RESULTS
The survey questionnaire was distributed to 21 centers (hospitals and institutions) that met the criteria as
above. Out of the 21 centers, only 13 centers responded and participated in this survey. The respondent rate
was 61.9% as in Table 1 below. In general, out of that 13 centers that participated in this survey, 38% was
from hospitals under the Ministry of Health, while the both Private Hospitals and University Hospitals was
31% as can be shown in Figure 1. The distribution of the imaging modalities among the centers was identified
based on types of camera involved in Nuclear Medicine Imaging; either Positron Emission Tomography-CT
Scan (PET-CT) and Single Photon Emission Computed Tomography (SPECT) or Gamma Camera. The
distribution was, out of 13 centers responded, 69% of them having only Gamma Camera or SPECT, 8% of
them having only PET-CT while 23% of the centers having both SPECT and PET-CT. The distribution is
detailed out in Figure 2.
Table 1: Respondent Rate
No. of Questionnaire No. of Respondent Respondent Rate (%)
Distributed (Hospitals / (Hospitals / institution /
institution / Centers) Centers)
21 13 61.9%
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University MOH MOH
Hosp / others 38%
Private Hospital
31%
University Hosp /
Private others
Hospital
31%
n = 13
Figure 1: Percentage Distribution of Respondent
PET-CT Both Gamma Camera /
8% 23% SPECT-CT
PET-CT
Gamma
Camera / Both
SPECT-CT
69%
n = 13
Figure 2: Percentage Distribution of imaging Modalities
A total number of 23 healthcare professionals participated in this survey and 52% of them are Nuclear
Medicine Physician /Specialist / Medical Officer, 31% of them are pharmacist (radiopharmacist) while 17% of
them are from other groups either technologist, radiographer or medical physicist. Result can be shown in
Figure 3.
Others Physician / Specialist /
(technologist Medical Officer
/radiographer )
Pharmacist
17%
Pharmacist Physician /
31% Specialist /
Medical
Officer
52%
n = 23
Figure 3: Percentage Distribution of Expertise Involved In the Survey
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Figure 4 shows the usage of medical radioisotope in General Nuclear Medicine Services (that involved in
Gamma Camera / SPECT Scan). Currently, there are 3 types of medical radioisotope used in General Nuclear
Medicine that are; Technetium-99m (Tc-99m), Gallium-67 (Ga-67) and Chromium-51 (Cr-51). The highest
usage is Tc-99m, where 8 centers currently utilize this radioisotope, followed by Cr-51 whereby 2 centers
involved in the utilization of it and lastly Ga-67 whereby only 1 center use this radioisotope.
The average Techntium-99m Generator order on weekly basis among the 8 centers was assessed. Figure 5
shows that 7 centers ordered an average of 500-1000mCi activity of Tc-99m generator per week with an average
cost of RM 52 500 per week, while only 1 center ordered a Tc-99m generator with an activity of more than
1000mCi per week with an average cost of RM 7 500 per week.
No. of Centre 8 1 2
9 Tc-99m Ga-67 Cr-51
8
7
6
5
4
3
2
1
0
8 7 52500 60000
7 500 mCi-1000 mCi
No. of Centre 6 50000 Cost (RM)
5 40000
4
3 30000
2
1 20000
0
1 7500 10000
> 1000 mCi
0
basis and how much cost (in Ringgit Malaysia) on average to obtain these
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As for PET Nuclear Medicine Services (that involved with PET-CT Scan Services), only two medical
radioisotope and radiopharmaceutical is currently in use that are Flourine-18 FDG and Gallium-68 Generator.
Figure 6 shows that 4 centres involved in the usage of Fluorine-18 FDG while only 1 centre use Gallium-68
Generator.
Fluorine-18 FDG utilization was assessed among these centers. Figure 7 show that 2 centers utilize Fluorine-18
FDG with an average activity of 100-200 mCi per order. While only 1 center utilizes Fluorine-18 FDG with an
average activity of 200-500 mCi per order. The average total cost were around RM 6 000 and RM 7 500 per
order.
No. of Centre 4
5
4
3
2
1
1
0 Gallium-68 Generator
Fluorine-18 FDG
3 2 6000 7500 8000
100-200 mCi 1 7000
2 200-500 mCi 6000
No. of Centre 5000
4000 Cost (RM)
1 3000
2000
0 1000
0
18F-FDG activity do your order and how much
cost (in Ringgit Malaysia) to obtain the 18F-
Figure 8 shows the trending of radioiodine usage in Malaysia. Iodine-131 has the highest usage among centers
where 8 centers involve in the utilization of it, while only 2 centers utilizes Iodine-131 MIBG
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9 8 2
8 Iodine-131 Iodine-131 MIBG
7
6
5
No. of Centre 4
3
2
1
0
The average Iodine-131 and Iodine-131 MIBG ordered on weekly basis were 4 200 mCi and 4.5 mCi. The
average cost were RM 84 000 per week and RM 15 750 per week for Iodine-131 and Iodine-131 MIBG as in
Figure 9.
4A5c0ti0vity (mCi) 4200 84000 Cost9(0R0M00)
4000 80000
3500 70000
3000 60000
2500 50000
2000 40000
1500 30000
1000 15750 20000
500 4.5 10000
0 Iodine-131 MIBG 0
Iodine-131
Figure 10 shows the usage of therapeutic radiopharmaceuticals among centers in Malaysia. The lists of
therapeutic radiopharmaceuticals are Yterium-90 (Y-90) Microspheres, Yterium-90 (Y-90) Synovectomy,
Rhenium-186 (Re-186), Irridium-192 (Ir-192) and Samarium-153 (Sm-153).
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4
3
3
No. of Centre 2 1 111
1
0
Y-90 Microsphere Y-90 Re-186 (bone Ir-192 Sm-153 (bone
Synovectomy pain palliation) (Brachytherapy) pain palliation)
at your center?
The average numbers of patients in the year2014 indicated for these therapeutic radiopharmaceuticals are as in
Figure 11. 21 patients indicated for Yterium-90 Microsphere, 51 patients indicated for Yterium-90
Synovectomy, 5 patients indicated for Rhenium-186 for bone pain palliation, 4 patients indicated for
brachytherapy using Irridium-192 while 2 patients indicated for Samarium-153 for bone pain palliation.
60
51
50
40
No of Patients 30 24
20
10 5 4 2
0
Y-90 Y-90 Re-186 (bone Ir-192 Sm-153 (bone
Microsphere Synovectomy pain palliation) (Brachytherapy) pain palliation)
Demand in medical radioisotope among General Nuclear Medicine Services as shown in Figure 12. Among the
radioisotope in demand are Technetium-99m (Tc-99m), Indium-111 (In-111), Gallium-67 (Ga-67) and
Chromium-51 (Cr-51). The highest demand are Technetium-99m (8 centers) followed by Chromium-51 (5
centers), Gallium-67 (4 centers) and lastly Indium-111 (2 centers).
47
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