Production of radioisotopes and radiopharmaceuticals at the Dalat nuclear research reactor

p. 
The target of tellurium dioxide contained in a 
welded aluminum capsule, according to the 
nuclear reaction as follows: 
The irradiated tellurium dioxide powder 
is transferred to a Vycor distillation vessel and 
connected to the iodine-131 tellurium 
processing system. The processing furnace is 
heated up to 750
o
C in order to distill the 
iodine-131 over to a charcoal column trap 
connected in-line of the distillation system. 
The charcoal column trap is rinsed with the de-
ionized water then eluted with sodium 
hydroxide 0.05N to form the final product of 
iodine-131 solution. The scheme in Fig. 10 
shows the flow chart of the operation and 
procedures. 
The target used in the production is an 
analytical grade material of natural tellurium 
as tellurium dioxide obtained from Fluka Inc. 
The chemical purity of the target as TeO2 is 
>95%. The specification of the target before 
being fired in a muffle furnace through 
analysis by emission spectrograph should 
contain of selenium less than 0.05% and 
heavy metals less than 0.1%. After being fired 
in the muffle furnace the analysis should give 
selenium less than 0.005% and heavy metal 
less than 0.1%. 
DUONG VAN DONG et al. 
51 
Fig. 10. The flow chart of the operation and procedures of I-131. 
Final product specification for use 
The final product as sodium iodide, 
131
I 
solution in NaOH, without reducing agents will 
be used as 
131
I bulk solution for 
radiopharmaceuticals production. The 
specification of the final product is as follows: 
Physical appearance: Colorless solution. 
Radioactivity of 
131
I: more than 11.1 
GBq (300 mCi) I-131/mL. 
133
I content: less than 0.80% of the 
131
I 
content at assay time. 
pH: more than 11 
Radionuclidic purity: 
131
I content more 
than 99.9%. 
Radiochemical purity: Iodide more than 95%. 
99mTc generator: 
Among the two reactions of choice for 
production of 
99
Mo parent isotope, the large 
investment for use of 
235
U(n, fission)
99
Mo 
reaction let us to opt for the 
98
Mo(n, ) 99Mo 
reaction to produce 
99m
Tc generator. 
In order to separate 
99m
Tc from its parent 
99
Mo we first used the MEK extraction method. 
The inherent disadvantages of this 
method compelled us to start our studies on the 
preparation of gel type generators in late 1984 
in the framework of the IAEA-CRP on the 
“Development of 99mTc generators using low 
power research reactor”. This represents the 
state-of-the-art for generator technology and 
promises opportunities for both developed and 
PRODUCTION OF RADIOISOTOPES AND RADIOPHARMACEUTICALS AT  
52 
developing countries particularly with respect 
to eliminating the need for fission 
99
Mo. Two 
directions of preparation of gel type generators 
were studied: 
- Preparation of chromatographic 
generators using zirconium molybdate (ZrMo) or 
titanium molybdate (TiMo) column packing 
materials synthesized from the neutron irradiated 
molybdenum trioxide and the zirconium chloride 
and/or titanium chloride, respectively. 
- Preparation of chromatographic 
generators using TiMo column packing material 
(preformed TiMo) synthesized from the inactive 
molybdenum compound and TiCl4 and 
subsequently neutron activated in the reactor. 
In both modes of preparation we have 
carried out studies on three different options of 
generators: 
- The chromatographic generator using 
0.9% NaCl solution as eluant. 
- The chromatographic generator using 
organic solvent as eluant Solid-Solvent-
extraction). 
- The chromatographic generator using dilute 
saline as eluant and 
99m
Tc concentration column. 
In the other hand, under the framework 
of Forum for Nuclear Cooperation in Asia 
(FNCA) program, the PZC based technology 
for production of 
99m
Tc- generator has been 
studied at DNRI as well as FNCA member 
countries in the past several years. 
PZC adsorbent of high performance for 
99
Mo adsorption was easy to synthesize from 
isopropyl alcohol (iPrOH) and ZrCl4. 
The procedures and relevant 
99m
Tc- 
generator designs for the preparation of PZC 
based 
99m
Tc- generators were successfully set 
up. The columns of from 1.0 gram to 4.0 gram 
weight of PZC and from 100 mCi to 500 mCi 
99
Mo could be used to produce portable, 
chromatographic type 
99m
Tc- generators which 
have a good performance for application in 
clinical investigations. Among the established 
procedures the column loading procedure was 
highly evaluated, because it proved to be 
prominent figures for easy and safe operation, 
for low cost of technology facilities, equipment 
and for the capability to match the traditional 
technology of the fission 
99
Mo based 
99m
Tc- 
generator production. 
DNRI had been proposed attending in 
these studies program. The commercial 
production of PZC generator through the 
establishment of national project stage 2006-
2008 for the routine production of 
99
Mo/
99m
Tc 
generator. In this project the 
99m
Tc-generator 
used PZC coming locally synthesis and from 
KAKEN - Japan as the column material, 
99
Mo 
formed from MoO3 irradiated at DNRR, the 
semi-automatic loading and adsorption machine 
had studied, designed and installed in the hot 
cells available. The generator assembly had also 
been designed and fabricated, (Figs. 11, and 12). 
Fig. 11. Schema of 
99m
Tc – Generator 
Design of commercial PZC-
99m
Tc generator 
DUONG VAN DONG et al. 
53 
Fig. 12. The semi-automatic loading machine 
In conclusion, it is strongly believed that 
ZrMo, TiMo and PZC based generator play an 
importance role as alternative technology for 
production of 
99
Mo/
99m
Tc generator from 
reaction 
98Mo(n, γ)99Mo. However these 
methods were not very appropriate for the low 
power research reactor as DNRR. Because of 
those reasons, it is necessary to build a new 
research reactor with power at least of 10 MW, 
and the neutron flux is high enough to research 
and produce radioisotopes. 
Phosphorus-32: 
32
P isotope was produced according to two 
nuclear reactions: 
32
S(n, p)
32
P and 
31
P(n, )32P. 
The first reaction was used for the 
production of injectable carrier-free 
32
P 
solution, the second for that of 
32
P –isotope 
applicators for skin disease treatment. 
First the injectable 
32
P solution of 
radioactivity of ten mCi scale was produced 
from irradiated MgSO4 target using magnesia 
as absorbent to separate 
32
P isotope from 
MgSO4 solution. In the case of Ci scale 
production, the large amount of waste 
produced from this technology caused 
storage problems. Recently, we have 
introduced the distillation technique to 
separate 
32
P from reactor irradiated elemental 
sulfur. Our glass apparatus for this 
production process is shown in Fig. 13. It can 
be used for distillation either in the vacuum 
or in the N2 gas flow by changing the upper 
stopper of the distillation vessel. The 
distillation parameters and post-distillation 
purification of 
32
P solution were adopted as 
described in literature. 
Fig. 13. The glass apparatus for 
32
P production 
process using nuclear reaction 
32
S(n, p)
32
P 
The 
32
P applicators for skin disease 
treatment were produced by neutron irradiation 
of a soft plate preformed from cloth binder and 
a covering mixture of red phosphorus and glue. 
After irradiation in the reactor, the radioactive 
plate was impregnated with plastic and covered 
with Scotch adhesive. The mechanical 
strength of the preformed plate was not lost 
under 75-hour irradiation in a thermal neutron 
flux of 5x10
12 
n.cm
-2
.s
-1
. Under this irradiation 
a plate containing 65 mg P per square 
centimeter gives a radioactivity of 15 mCi 
32
P. 
The absorbed dose rate on the surface of the 
plate of size 50 x 40 mm
2
 was measured as 110 
Rad.min
-1 
at the center and 75 Rad.min
-1 
on the 
edge. Medical doctors’ experience over ten 
years showed that with repeated treatment of 
three or five 15-minute applications the 
following diseases will be cured: Eczema, skin 
cancer, bump scar, etc. At present more than 
75 Ci 
32
P in applicator form are used annually 
in the country. 
PRODUCTION OF RADIOISOTOPES AND RADIOPHARMACEUTICALS AT  
54 
Cr-51 isotope: 
The production of 
51
Cr isotope was 
carried out based on the Szilard-Charmel 
reaction using reagent grade K2CrO4 target. 
The chemical separation of recoiled 
51
Cr 
nuclide was based on the selective adsorption 
of this isotope on an inorganic ion exchanger 
Si-ZrP (Silica gel supported zirconium - 
phosphate) synthesized by us. 
Other isotopes were also produced 
when requested in small amounts for industrial 
and agricultural applications. The methods for 
production of these isotopes were selected 
from investigation results or different reference 
sources. 
D. Production of Kits for labelling with 
99m
Tc: 
In furthering the application of 
99m
Tc 
isotope, the local availability of Kits for 
labelling with 
99m
Tc plays an important role. 
With IAEA support the basic equipment for the 
production of Kits has been installed in our 
laboratory. At present many kinds of in-vivo 
Kits have been successfully prepared and put 
to use in the country, they are Phytate, 
Gluconate, Pyrophosphate, Citrate, DMSA, 
HIDA, DTPA, Maccroaggregated HSA and 
EHDP (1-hydroxy ethylidene-1, 1-disodium-
phosphate). 
The studies on the preparation of 
Radioimmuno-assay Kits and therapeutic 
agents and/or radionuclides were also carried 
out. The future production of the above 
mentioned items is foreseen and planned. 
E. Quality control 
Radioisotope and radiopharmaceutical 
quality control was carried out for all batches 
of our products. The gamma spectrum analysis 
using Ge-Li detector coupled with a 
multichannel analyser is used for radionuclide 
purity control, the TLC, HPLC and gel-
chromatography techniques for chemical 
purity, and the spectrometry and neutron 
activation analysis for chemical purity. 
Biodistribution assay, biological tests 
(apyrogenity, sterility, toxicity) and 
physicochemical tests (pH, turbidity) are also 
carried out regularly. 
Fig. 14. HPLC system for QC. 
III. LOCAL PRODUCTION VOLUME 
AND DEMAND 
These types of radioisotopes have 
regularly been supplied to more than 25 
hospitals in Vietnam two times per month. The 
131
1 radioisotope labelled radiopharmaceuticals 
such as 
131
I-Hippuran; 
131
IMIBG have also 
been regularly supplied to hospitals. 
Radioisotope production rate is shown in Fig. 
15 and Table I. 
In order to support the application of 
99m
Tc, 
113m
In, 
177
Lu and 
153
Sm radioisotopes in 
clinical diagnosis and therapeutics, the 
preparation of radiopharmaceuticals in Kit 
forms has been carried out. The following Kits 
have regularly been manufactured in DNRI: 
Phytate, Gluconate, Pyrophosphate, Citrate, 
DMSA, EHIDA, DTPA, HSA 
macroaggregated, HEDP, HmPAO, MIBI, 
MDP. 
DUONG VAN DONG et al. 
55 
Radioimmunoassay Kits: The RIA Kit 
production and distribution programme have 
also started. T3 and T4 Kits have been selected 
locally by end-users with a share of 50% of 
domestic market. Other RIA and IRMA Kits 
can be supplied to end-users by dispensing 
process based on the contract. 
Fig. 15. Total activity of radioisotopes produced 
at DNRI 
Fig. 16. Radioisotopes and Radiopharmaceuticals 
produced at the DNRI 
Table I. The supply/demand for radioisotopes and diagnostic Kits in Vietnam. 
Product Supply Demand at present 
131
I- Diagnostic and 
therapeutic capsule/solution 
20-30 Ci/month 
40-50 Ci/month 
99m
Tc-Generator 10 generators (200-
500mCi/each)/month 
40 generators (200-
500mCi/each)/month 
32
P-Solution/ 
Applicator 
50 Ci/month 50 Ci/month 
Kits for 
99m
Tc-Labelling 
- MDP 
- DTPA 
- DMSA 
- PHYTATE 
- Orther 
400 Kit/ month 
200 Kit/ month 
200 Kit/ month 
200 Kit/ month 
200 Kit/ month 
500 Kit/ month 
300 Kit/ month 
300 Kit/ month 
300 Kit/ month 
300 Kit/ month 
IV. THE APPLICATION OF LOCAL 
PRODUCTS IN THE COUNTRY 
- Number of nuclear medicine 
departments in Vietnam: 25 
These departments almost are located in 
the big cities of the country (Fig. 17). 
- Number of gamma cameras (planar 
and SPECT): 22 
- There are six centres of PET-CT and 
cyclotron in Hanoi Capital and Ho Chi Minh 
City. 
- Radiopharmaceuticals used in these 
centres: Na
131
I solution and capsule, Sodium-
(
99m
Tc) pertechnetate (
99m
Tc-Generator) 
131
I-
Hippuran, Sodium-(
32
P) orthophosphate, 
131
I-
MIBG, In-vivo Kits (MDP, DTPA, DMSA, 
PRODUCTION OF RADIOISOTOPES AND RADIOPHARMACEUTICALS AT  
56 
Phosphon, Glucon, Phytate, MAHSA, EHIDA, 
HMPAO, MIBI, MAG-3, etc.). 
- Locally manufactured products take 
about 50% of total market. In order to get a 
higher market share now we increase the 
production by loading generations with 
importing raw materials such as 
99
Mo and 
131
I 
solutions. 
Fig. 17. Location of Nuclear Medicine Departments 
in Vietnam. 
REFERENCES 
[1] Le Van So, Production of 99mTc isotope from the 
chromatographic generator using zirconium-
molydate and titanium-molybdate targets as 
column packing materials. Research Co-
ordination Meeting, Bandung, Indonesia, 
(October 1987). 
[2] Radioisotope production and quality control. 
Technical Reports Series No. 128. IAFA, 
Vienna, (1971). 
[3] Le Van So, Investigation on the silica gel 
supported form of micro crystalline zirconium-
phosphate ion exchanger and its applications in 
chemical separation. 
 I.- Preparation, ion exchange properties and 
stability of Si-ZrP, J. Radioanal. Nucl. Chem., 
(Articles) 9 (1) 17-30 (1986). 
[4] Le Van So, Richard M. Lambrecht, 
Development of alternative technologies for a 
gel-type chromatographic 99mTc generator. J. 
Labelled Compd. Radiopharm. 35:270 (1994). 
[5] Ngo Quang Huy et al, Reactor physics 
experimental studies on Dalat nuclear research 
reactor, 50A-01-04 Research Project Final 
Report, (1990) (in Vietnamese). 
[6] Tran Ha Anh et al, Studies on Dalat Nuclear 
Reactor Physics and Technique and on 
Measures to ensure the safety and efficiency of 
the reactor, KC-09-15 Research Project Final 
Report, (1995). 
[7] Nguyen Nhi Dien, Dalat nuclear research 
reactor - status of operation and utilization, 
Dalat Sym. -RR-PI-05, Dalat, (2005). 
[8] Duong Van Dong, Status of Radioisotope 
Production and Application in Vietnam, Dalat 
Sym. -RR-PI-09, Dalat, (2009). 
[9] Duong Van Dong, Status of the study on PZC 
based Tc-99m generator and potential of its 
commercial production in Vietnam, Nihon 
Genshiryoku Kenkyu Kaihatsu Kiko JAEA-
Conf, Journal Code: L2150A, page 25-29 
(2007).