1. SEPARATION OF HEAVY OXYGEN ISOTOPES.
A SURVEY
Gheorghe VASARU
National Institute for Research and Development
of Isotopic and Molecular Technologies,
Cluj-Napoca, ROMANIA
gvasaru@hotmail.com

2. Oxygen isotopes
• Oxygen is a mixture of three stable
isotopes:
• 16O (99.757 at. %),
• 17O (0.038 at. %)
and
• 18O (0.205 at. %), respectively.

3. Applications and needs of oxygen isotopes
• Stable isotopes of oxygen have a wide
range of applications in almost every
natural and physical science. The most
notable uses of oxygen isotopes are in the
fields of agronomy, marine biology,
environmental science, nutrition,
biochemical research, medical diagnostics
and medical therapy. All three stable
oxygen isotopes have medical
applications:

4. 16
O
• 16O is used in the production of radioactive
13
N which is used for Positron Emission
Tomography (PET) imaging and
myocardial perfusion.

5. 17
O
• 17O can be used as a tracer in the study of
cerebral oxygen utilization. Compounds
labeled with 17O (nuclear spin I = 5/2) are
used in Nuclear Magnetic Resonance
(NMR) experiments. Researches are
currently exploring the use of 17O to
provide improved lung images.

6. 18
O
• 18O is an important precursor for the
production of fluorodeoxyglucose (FDG)
used in PET. Generally, in the
radiopharmaceutical industry, enriched
water (H218O) is bombarded with hydrogen
ions in either a cyclotron or
linear accelerator creating 18F. This is then
synthesized into FDG and injected into a
patient.

7. 18
•
O
O is a key isotope because it is the raw material for cyclotron
production of 18F used to produce 2-[18F] fluoro-2-deoxyglucose
(18FDG) - a very important a tracer in PET. For this purpose, H 218O is
used as a precursor. To produce these scans 18FDG is needed. To
do this, 18O enriched water, (95 % or 97 %), is proton bombarded in
a cyclotron to produce fluorine 18F that is then used in the production
of 18FDG in an automated radiochemical synthesis. The 18FDG is then
injected into patients as an intravenous diagnostic
radiopharmaceutical. The PET scan is then performed on the
patient. Millions of these FDG-PET medical procedures are
performed annually to investigate a range of diseases in various
human organs.18O enriched water, (10%), is also used in medical
research for energy expenditure studies. This research measures
the amount of food that is being metabolized by a person and is
often used in cholesterol research.
18

8. 18
O
• Demand for highly enriched 18O skyrocketed with
the breakthrough of PET scans, in which the
compound is used by doctors to view soft tissue
and bone images as well as respiratory and
circulation functions. PET scans provide a more
precise color image of the body in order to
diagnose tumors and other critical organ
problems. 18O is also used in the metabolic
research community to measure energy
expenditure and body water consumption

9. PET
• PET is an imaging technique which assists in the
diagnosis of many diseases in areas such as
oncology, neurology and cardiology. PET allows
the physician to examine the whole patient at
once, by producing pictures of the functions of
the human body unobtainable by other imaging
techniques. These images show body
metabolism and other functions rather than
simply the gross anatomy and structures
revealed by conventional X-rays, CT or MRI
scans.

10. PET
• Detailed Product Description
• With the growing demand for PET scans as a
diagnostic tool for physicians, 18O enriched water
has become increasingly important.
• To produce these scans 18FDG is needed. To do
this, 18O enriched water at 95% or 97% is proton
bombarded in a cyclotron to produce 18F that is
then used in the production of 18F FDG in an
automated radiochemical synthesis. The 18F FDG
is then injected into patients as an intravenous
diagnostic radiopharmaceutical. The PET scan
is then performed on the patient.

11. 18
O
• 18O is also used as a tracer for several
biomedical applications. The two primary
applications are the study of organism energy
expenditure and organ specific utilization of
glucose.
• With the growing demand for PET scans as a
diagnostic tool for physicians, 18O water has
become increasingly important. This application
accounts for the vast increases in world-wide
consumption of 18O.

12. II. Oxygen Isotope Separation Methods
•
•
•
•
•
•
•
After the discovery of the 17O and 18O isotopes, numerous attempts were
made to obtain oxygen containing materials enriched in these isotopes.
These processes include fractional distillation of water, of liquid oxygen, of
carbon monoxide, of nitric monoxide or organic liquids, thermal diffusion of
oxygen, electrolyses of water, membranes, chemical exchange reactions
and laser methods.
Of all these processes only few have been found promising as methods of
obtaining considerable amounts of highly enriched oxygen isotopes. There
are:
- fractional distillation of water,
- distillation of water combined with thermal diffusion of oxygen gas,
- cryogenic distillation of nitric oxide,
- fractional distillation of carbon monoxide and
- thermal diffusion of oxygen.
The latter process has yielded the highest concentration of 18O obtained,
over 99.5 %. As a consequence, however, of the low throughput of
thermal diffusion columns this method is not particularly suitable for the
production of 17O and 18O in quantities of gram per day.

13. Process Materials
• Water, oxygen and nitric oxide were considered
as process materials. The use of oxygen,
instead water, involved a larger capital
investment and offered few compensating
advantages. Nitric oxide was potentially
attractive because of the relatively large
differences in the vapor pressures of its isotopic
species. The equilibrium distillation of water was
tentatively selected as the method of producing
high purity 17O.

14. IBakhtadze (IAEA, Leipzig – 1977).
IAEA –Modern Trends in Biological Applications of SI, Leipzig, 1977
A.B. Bakhtadze, TC – 90/1 – Separation of SI : A Review
•
•
•
Research on the separation of SI and the investigation of their
properties was started 70 years ago. Up to 1955, however, research
on the separation of the SI of oxygen was limited to a laboratory
scale.
In subsequent years (1955 – 1965) interest in these isotopes
increased considerably. In many laboratories throughout the world
complex investigation were started to develop effective methods for
their extraction and use in various field of science, industry and
agriculture. In a number of countries, specialized scientific research
institutes were established.
Numerous studies in many countries have shown that distillation
and chemical exchange are the most promising methods for
extracting the SI of oxygen. Starting in 1965, 18O has been produced
in yearly amounts within the range of several hundred grammes

15. Data on enrichment plants for
oxygen isotopes production, 1977 [1]
Isotope
Country
Ref
H2O distillation
98
5.6
H218O
Israel
[1,55]
95
Some kg
H218O
Germany
[1]
25
UK
[6]
0-99
95-99
90
1.5
2
1.85
USA
USA
SU
[1,43]
H2O distillation
2026
1.8
Israel
[1.55]
D217O distillation
O
Product
form
NO distillation at
low temp
17
Production
(kg/an)
O2 distillation at
low temp.
O
Isotope
conc. (at
%)
Distillation
18
Separation
method
99.8
Germany
[1]
0.3
USA
[1.43]
2700-3500
40
USA
SU
[43]
NO distillation at
low temp
16
O
NO distillation at
low temp
99.99
99.9
18
O2
H218O
H218O
H218O
[1]

16. Los Alamos National Laboratory (LANL)
• LANL pioneered the process of stable isotope production
using the cryogenic distillation separation method in the
late 1960’s.: 17O and 18O was produced by cryogenic
distillation of nitric oxide at ICON plant.

17. • In USA, the first three stages low
temperature distillation of NO has been
realized in 1965 by Mc. Inteer et al.
(Cascade length: 57.5 m.; Column
diameters: 52.5 mm.,23.6 mm., 17.3 mm.,
respectively.). After a repeated
rectification in a column of 5.8 m length
and 10.9 mm in diameter, has been
attained concentrations of 98.2 at % 18O
and 8.3 at. % 17O respectively)

18. ICON facility, Los Alamos National
Laboratories (LANL)

19. Cambridge Isotope Laboratories (CIL)
• CIL (U.S.): 18O water distillation plant located in Xenia,
Ohio. The expanded plant produces 250 Kg/y of 18O used
for the production of FDG in the PET industry and in
other medical research.

20. CIL
Xenia
Ohio
USA
CIL has been
producing 18O
water for the
PET community
since 1996.
The expanded
plant produces
250 Kg per year
of 18O used for
the production
of FDG in the
PET industry
and in other
medical
research.

21. 2001 ICON
• Lease agreements to be signed today between the
Department of Energy, the Los Alamos Commerce and
Development Corp. and Spectra Gases of New Jersey,
will pave the way for a private company to begin
producing the potentially life-saving stable isotopes of
17
O and 18O for the U.S. market. Production will occur at
the Laboratory's ICON facility. ICON stands for Isotopes
of Carbon, Oxygen and Nitrogen.
• The company plans to upgrade some of the equipment
at the ICON facility before beginning production of
carbon and oxygen isotopes. 17O and 18O will be produced
by cryogenic distillation of nitric oxide, while 13C will be
produced from carbon monoxide.

22. Icon
• Application of the stable isotopes of oxygen (17O and 18O)
are useful in studies of cell and tissues by nuclear
methods and mass spectrometry especially for the
investigation of water molecule in normal and cancerous
cells.
•
Conclusion: Successful research has shown that
kilogram quantities of the isotopes of oxygen (ICONS)
will be needed for clinical applications concerned specific
diagnostic tests and organ dysfunction. As compounds
labeled with oxygen become less expensive and
commercially available, it is expected that biomedical
applications of these isotopes will increase.

23. CIL, Xenia, Ohio, USA

24. CIL, Xenia, Ohio, USA
High Columns

25. December 18, 2002 Groundbreaking Ceremony for CIL Isotope
Separations, Inc. Another 18O Facility Expansion
•
•
In January 2000, CIL announced construction of the world's largest
isotope separation facility for the production of highly enriched 18O.
CIL has made this commitment in order to provide a solution for the
current shortage of 18O water. Increasing demands for highly
enriched (96%) 18O water have come from the international PET
community and for 10% 18O water from the metabolic research
community. By building this new facility, CIL hopes to ensure that
ample supplies of 18O will be available for all important research
needs and diagnostic efforts for the foreseeable future.

26. Global Scientific Technologies (GST)
• GST, is a St. Petersburg, Russia - based
manufacturer of 18O used to produce PET
radiopharmaceuticals. GST is one of the world’s
largest producers of 18O .

27. GST 1
•
•
GST is main producer of water 18O. GST was established in 1995. Situated
in Sosnovy Bor town, near Saint- Petersburg, Russia. The company is
standing for developing of global scientific research. GST have a great
experience in producing 18O - water. GST is one of the world's leaders in
producing 18O - water used in Positron Emission Tomography (PET). GST is
close connected with leading Russian Physical and Medical Institutions,
such as Institute of Human Brain, Central Radiological Institute, V.G.Khlopin
Radium Institute (Saint- Petersburg) , Russian Research Centre Kurchatov
Institute, Central President's Moscow Hospital, Backulev Cardiological
Center. GST has been working for a long time with Isonics Corporation
(USA, Colorado.
Global Scientific Technologies CMR-GST is one of the world leaders in
production 18O enriched water. Situated in Sosnovy Bor Town near
St.Petersburg, Russia. 18O - water used in cyclotron target for production of
18
F labeled compounds for Positron Emission Tomography (PET).
Everywhere it obtained the highest appreciation for quality and the highest
yield for FDG (Fluorodeoxyglucose). Our 18O - water has more 97.0 atom %
Isotope Enriched 18O.

28. GST2
•
•
•
•
Current production quality control of provided on plant's laboratories in
Sosnovy Bor. Final quality control and issue of Quality Certificate made in
Moscow independence laboratories of Kurchatov Institute and Moscow
State University.
Production of 18O - water is made over 10 years and annual volume
reaches 80 kg. And supplied to head's PET centers of US, Europe and Asia.
Oxygen is a mixture of 3 stable isotopes: 16O (99.759 atom%), 17O (0.037
atom%) and 18O (0.204 atom%). Natural water is a mixture of low boilingpoint compound H216O with temperature of boiling point - 100ºC. And high
boiling point compound H218O with temperature of boiling - 100.15ºC.
Separation of mixture H216O and H218O carried out in a series of distillation
columns. Each column consists of cube-evaporator and self-column with
special packing, condenser, and upper reservoir. Steam lift up in the column
and interact with water which floating down the packing in film form. At that
stage occurs mass exchange process. When steam is getting depleted and
steaming down water enriches with high boiling point compound H218O.

29. GST3
•
•
•
•
Enriched water till 97% 18O - water passes stage of purification of
deuterium (normalization) till such physics-chemical parameters that
meet requirements of using in PET centers.
In the heart of method purification lies decomposition of water on 18O
and hydrogen, with next purification of 18O and synthesis of 18O water from 18O and purified hydrogen, received from natural water.
Main parameters of enriched 18O - water are tested routinely during
the production process. The quality of each final batch of 18O - water
tested in independence laboratories that have international
certification. For each batch independents laboratories make new
quality certificate and signed by heads of this laboratories.
The isotope content on a gas was determined by mass
spectrometer ionization impact МИ-1201В. Accuracy for 18O is ± 0.2
atom %, for enriched higher than 80 atom %.

30. GST Plant 1

31. GST Plant 2

32. Dostrovsky,
•
•
•
Dostrovsky, A. Raviv: Separation of the Heavy Isotopes of Oxygen
by Distillation
(Proc. of the Symposium on Isotope Separation, Amsterdam, 1957,
p. 336).
Following the discovery of 18O by Giauque and Johnston [1],
numerous attempts were made to obtain oxygen containing
materials enriched in this isotope. This oxygen isotope excited
particular interest among chemists as a possible tracer in the study
of the very many reactions involving an oxygen bond. In the course
of time all known processes which lead to isotope fractionation were
tested for their suitability for oxygen isotopes enrichment. These
included fractional distillation of water [2], of liquid oxygen [3-5] of
carbon monoxide [6] or organic liquids [7-9], thermal diffusion of
oxygen [10-15], electrolysis of water [17-22] and chemical exchange
reactions [23-27].

33. Water distillation
• The first researches for enrichment of 18O by water
distillation has been performed by Dostrovsky in Israel
[54}. The industrial plant for production of oxygen
isotopes by water distillation (of natural isotopic
concentration) and thermal diffusion, has been
constructed at Weizmann Institute [1,55]. It consisted of
two sections. The first, consisting of 27 columns (inner
diameter of 100 ÷ 17 mm., each with a length 0f 10 ÷ 15
m. Thermal diffusion section consisted of 104 columns
with an inner diameter of 12 mm and length of 1.5 m.
The production of this plant was of 5.5 kg/y oxygen at
concentration of 98.5 at. % 18O and 0.9 kg/y of 20 at. %
17
O respectively. Thermal diffusion section facilitated
enrichments of 99.9 at. % 18O and 96 at. % 17O,
respectively.)

34. Prof. Dostrovski

35. Marshall Isotopes Ltd. (Israel)
• The technology used in the plant is the fractional
distillation of water; main products - the 95% and the
10% 18O-enriched water, respectively.

36. MARSHALL
ISOTOPES LTD
Israel
founded in 1998
2000 … 30 kg/y
2002 … 60 kg/y
2004 … 100 kg/y
Every company whose core business is technology devotes
considerable resources to R&D. Marshall Investments profit and
loss statement does not contain this item, because the company's
technology know-how is held by
Prof. Michael
Epstein, formerly of the Weizmann Institute of Science.

37. ISOTEC (US)
• - Was the first commercial company to build and
maintain cryogenic distillation columns for the separation
of 18O. Isotec is also the first commercial company to
build and maintain thermal diffusion columns for the
production of noble gases and oxygen isotopes. It
continually explores alternative separation methods such
as laser separation and chemical exchange. Isotec is the
largest commercial producer of water- 18O and gas by
cryogenic distillation of nitric oxide since 1985 at
concentrations up to > 99 atom %.

38. ISOTEC
has the world’s largest
18
O production capacity, and
has been enriching 18O by
cryogenic distillation of nitric oxide
since 1985.

39. ISOTEC
October 30, 1998
ISOTEC has started construction of
additional 18O capacity to greatly
increase its total production of oxygen18 isotope. Isotec expects the expansion
to increase output beginning in mid 1999
and again substantially in 2000 and
2001 to meet worldwide demand.

40. Isotec facility, Miami Township, Ohio

41. LANL developed isotope
separation using
NO distillation technology.
Isotec acquired
the technology for commercial
use.
Sigma–Aldrich purchased the Isotec
facility in 2001 from Matheson Gas Products.

42. September 24, 2003
According to Isotec General Manager
Diane Szydel, half to three quarters
of the 180 water that the plant was
producing came from a carbon
monoxide process that was
unaffected by the explosion of a nitric
oxide tank. "The CO columns were
not affected at all," she said.

43. 20-foot-diameter, 8-foot-deep crater and structural
damage caused by NO process unit explosion

44. ISONICS Corporation (Nasdaq:ISON)
•
•
Is the world’s second largest supplier of 18O.
18
O represents ISONICS single largest product line and is used in medical
cyclotrons to produce the primary radioisotope currently used in PET. Due
to its ability to identify and localize areas of high metabolic activity, PET has
been demonstrated to be one of the most powerful tools in the fight against
many types of new and recurrent cancers. The demand for 18O continues to
grow rapidly as the number of approved clinical procedures increase and
insurance reimbursement treatment remains favorable. As the tight supply
situation currently existing is likely to persist for the next several years,
ISONICS will continue its aggressive efforts aimed at quickly increasing its
production capacity.

45. ROTEM Industries (Israel)
.
•
•
•
•
•
•
Is the world largest manufacturer of 18O enriched water, an intermediate bulk material
used in a cyclotron water target in the production of 18F labeled compounds for PET
diagnostics in nuclear medicine.
The process used for the enrichment of the 18O and 17O isotopes of oxygen is water
fractional distillation
Use is made of the very slight difference in the vapor pressure of the isotopic forms of
water. Fractional distillation is carried out in a series of distillation columns, each filled
with a special, proprietary packing endowing it with a very high separation power.
The enrichment is carried out in stages, enabling ROTEM to offer water of any
desired enrichment level , from 2 atom. % to 95 atom. % .
After distillation, which enriches the water also with deuterium oxide, a normalization
step takes place, where the water is electrolyzed and the resulting 18O gas is reacted
with electronic grade hydrogen to re-form water of extremely high quality.
For the 95 atom. % water, mostly intended for PET, a further purification process
combining ultra - filtration, distillation and terminal heat-sterilization is carried out in a
controlled environment to produce sterile and non-pyrogenic water.

46. Rotem
Industries
Ltd.,
Israel
O output will increase to
120 kilograms in 2003
and
250 kilograms in 2005.
18

47. Huayi Isotope Co. (HIC),
• Huayi Isotope Co. (HIC), located near
Shanghai in China, is one of the largest 18O
manufacturers in Asia , with a yearly capacity of
100 kg and offers the nuclear medicine
community the highest quality greater than 98%
18
O enriched water for use in the production of
radiotracer 18F (FDG), and 10% single water or
double-labeled water for metabolism studies of
body energy expenditure while in full compliance
with GMP standards and certified by ISO9001:2000 and ISO-14001.

48. Huayi Isotope Co. Shanghai, China

49. SRICI
•
Shanghai Research Institute of Chemical Industry (SRICI) is the
world leader in the separation of 15N isotope and China leader in the
separation of 18O for medical applications and the production of
stable isotope labelled compounds. From the 1960's, SRICI began
the research on separating 2H, 15N, 13C, 22Ne ... etc. In 2000 SRICI built
the world's largest 15N separation facility, which has met the 60% 15N
needs of worldwide consumers. In 2002 SRICI took cognizance of
the extensive need of the Positron Emission Tomography (PET) and
began the research on separating 18O. SRICI constructed its first 18O
water distillation plant in China. This plant meets advanced world
standards and now has an annual production capacity of 50 Kg, and
probably has been expanded to 100 Kg per year from 2006. With
his breadth of experience and expertise in stable isotopes, SRICI is
very sure of itself to satisfy the growing global needs of the PET
community for consistently high quality product delivered on time at
a fair price. The product type of SRICI is 18O - water (18O > 95 %).

50. SRICI's 18O Milestones
•
•
•
•
•
•
•
•
•
- 1957 - SRICI's beginning of the research on the separation of heavy (deuterium)
water
-1959 - Success in the research, and get the heavy (deuterium) water which
abundance is 99.999%
- 2000 - SRICI's beginning of the research on the separation of heavy (oxygen-18)
water
- 2002 - Success in the research on the water distillation of heavy ( oxygen-18 ) water
and get the heavy (oxygen-18 ) water which abundance is 10.0%+(deuterium)
- 2003 - SRICI build up the China first manufacture of the heavy (oxygen-18)
water
- 2004 (April) - SRICI's manufacture get the certified heavy
( oxygen-18 ) water,which abundance is 99.0%+ ( oxygen-18)
- 2004 (June) - SRICI's certified heavy ( oxygen-18 ) water,which abundance is
95.0%+ (oxygen-18) is successfully used in PET, and distributed to worldwide
community
- 2004 (August) - SRICI's capacity is up to 50Kg/y heavy (oxygen-18) water,which
abundance is 95.0%+( oxygen-18)
- 2005 (Jan) - SRICI's certified heavy ( oxygen-18 )water,which abundance is 97.0%+
( oxygen-18) is distributed to worldwide community

51. SRICI – Botles with18O - water

52. SRICI Shanghai, China

53. SRICI R & D Team

54. Medical Isotopes, Inc., Pelham, NH, US
• Supply 18O enriched water at 97%; 95% and 10%
respectively to the medical community.
• 18O enriched water at 95% and the 97% is used for PET.
• The 10% 18O - water is used in patients for metabolic
studies.
• 18O enriched water, 10% is used in medical research for
metabolic studies. This research measures the amount
of food that is being metabolized by a person and is
often used in Cholesterol research.

55. Remarques
•
•
•
The capacity of these commercial producers is not always directly available. These
producers isolate 18O by distillation of water or nitric oxide using large, steady state
distillation columns. Commercial quantities are however, produced by fractional
distillation of water or cryogenic distillation of nitric oxide or carbon monoxide.
Development of a variety of isotope separation processes is an important R&D
activity, because there is no one isotope separation process which is economically
superior to all others for every isotope. The best method of separation can be chosen
only after an evaluation of the chemical and physical properties of nuclides involved,
the degree of separation desired, the scale of the operation, the capital investment,
the energy consumption, and the operating and maintenance costs for each
competing separation process. The availability of a variety of isotope separation
methods also allows the option of combining two or more processes for a more
economical isotope production.
This paper reviews succinctly the various methods used for separation of heavy
stable isotopes of oxygen. In Appendix, a selected bibliography are given, with a
comprehensive compilation of references from the scientific and technical literature
on the separation of heavy oxygen isotopes. The references are arranged
chronologically according to the leading author.

56. Leipzig 1977: Summary Report
• In recent years there has been a pronounced
increase in the use of stable isotopes in the life
sciences, particularly oxygen isotopes. This is
due to the increased availability of these
isotopes in a wider variety of useful chemical
forms and the increase in the sensitivity,
selectivity and reliability with which these
isotopes can be analyzed by mass
spectrometry, optical emission spectroscopy,
nuclear magnetic resonance spectroscopy and
other methods.

57. Leipzig 1977: Summary Report
•
•
•
Current status and present problem. Substantial progress has been
made in the recent years in developing methods for separation of
stable isotopes of oxygen. Until 1977, the principal methods of
separation of 16O, 17O in current use was distillation of NO, H2O,
(enrichment of product: 99.98-99.99 at % for 16O and 20-40 at % for
17
O at a world production of 1000s, respectively 2-5 kg/y).For the 18O
- distillation of NO,H2O,D2O at enrichments of 90-99.99 at % and a
production of 15-20 kg/y.
Despite the fact that separation methods for oxygen isotopes are
fairly well advanced, it is still of interest to consider how costs may
yet be further reduced. The main possibilities are (1) the further
optimization of process in existing plants, (2) the design of new
separation plants, perhaps based on new compounds and additives,
and (3) increasing the scale of production.
The separation of oxygen isotopes is best carried out in large
industrial-type units serving a wide geographical area.

58. •
Of all these processes only three have been found promising as
methods of obtaining considerable amounts of highly enriched
oxygen isotopes. There are: a. the fractional distillation of water, b.
the fractional distillation of carbon monoxide and c. thermal diffusion
of oxygen [10-11]. The latter process has yielded the highest
concentration of 18O obtained to date – 99.5 %. As a consequence,
however, of the low throughput of thermal diffusion columns this
method is not particularly suitable for the production of 18O and 17O in
quantities of gram per day. The low temperature distillation of
carbon monoxide has been used at Harwell [6] for many years and
reasonable production of both 18O and 13C have been achieved.
Dostrovsky et al., have been studying the enrichment of oxygen
isotopes by the fractional distillation of water for over 10 years [2935].

59. • Fractional distillation of water has been a favorite
process since early days of interest in 18O. The first
attempt at a relatively large scale production was made
in 1936 by Huffman and Urey [36-37] who obtained
some hundreds of grams of water enriched 5 times with
respect to 18O. Fractionating columns for 18O has also
been constructed by Brodsky and co. [38-39] and later
by Baertschi and Kuhn [40]. After World War II, large
quantities of 18O water of about 1.5 % concentration
became available in USA, presumably as a by- product
of heavy water production.

60. • New results obtained in biological and medical
investigations with 18O as well as the success in
developing methods for measuring isotope composition
(MS, NMR, spectrometry, etc.,) have led to a new and
greatly increased spectrum of isotope use.
• The problem has therefore arisen of producing isotopes
and labeled compounds in amounts of hundreds of kg at
considerably lower price.
• In this connection in the last 40 – 45 years, attention has
been focused on increasing the scale of existing
methods. In this period some very effective methods
have been established for enriching 17,18O. For example:

61. •
•
•
•
•
•
•
•
O - by low-temperature distillation of nitrogen oxide (USA:
1,5 kg/y 18O (at concentrations of 95-98%); USSR: 2,5 kg/y 18O
(90%);
- by water distillation (Israel, with a yearly capacity of: 3 – 4 kg/y
18
O (99%); Germany);
- by cryogenic distillation of oxygen ( Daniels, W.R. et al.,
England).
18
Steps :
- Determination of elementary separation factor for distillation of
different compounds containing oxygen. For practical purposes: NO,
O2 and water
- Elaboration of technological processes which use these
compounds.
- The first paper relative to simultaneously production of 15N, 17,18O
was of Clusius and Schleich) (1958, 1961) [47-46]?

62. •
•
•
In Soviet Union (now Russia) the researches about distillation at
low temperatures of NO has been performed by Asatiani et al., in
Tbilisi (1965, 1967) [49-50].. Using a two columns cascade an
enrichment of 18O at 90 at. % has been obtained. Later, (1977), an
industrial pilot plant for the distillation of nitric oxide has been
constructed. The plants consisted of a profiled stepped cascade
formed of terraced separation columns with a total length of 40 m
(Diameter and length of columns: 57 mm and 15 m; 32 mm and 13
m; 15 mm and 12 m respectively).
Distillation has been performed at a pressure a little above
atmosphere. The production of 18O was of several kg/y, at an
enrichment of 85-90 at. %.
In 1977, a nitric oxide distillation plant at low temperature produced
3.8 kg/y of 18O at concentration of 95 at. %).

63. •
•
•
•
•
•
In 1967, in the Karlsruhe nuclear research center (Germany) has
been operated a water-deuterated plant for enrichment of 17,18O. The
research activity has been performed in collaboration with norvegian
scientists [1,56]. The enrichment attained was 99.8 at % H 218O and
99 at % H217O respectively..
The 18O has been obtained by rectification of molecular oxygen. The
separation factor was greater than in the case of water but smaller
than for nitric oxide.
In UK, Prochem Co. constructed a plant for production of 18O by
rectification of molecular oxygen [6] it consisted from columns with
diameters of 37,5 ÷ 18,5 mm and 11 m length. This plant permitted
an enrichment of 25 at % 18O.
In the period of 1960, for separation of oxygen isotopes has been
proposed the exchange chemical reaction NO – water
N16O + H218O <=> N18O + H216O
of which elementary separation factor was of only 1.02 [60]

64. Data on enrichment plants for
oxygen isotopes production, 1977 [1]
Isotope
Separation
method
Isotope
conc. (at
%)
Production
(kg/an)
Product
form
Country
Ref
18O
H2O distillation
98
5.6
H218O
Israel
[1,55]
Distillation
95
Some kg
H218O
Germany
[1]
O2 distillation at
low temp.
25
18O
2
UK
[6]
NO distillation at
low temp
0-99
95-99
90
1.5
2
1.85
H218O
H218O
H218O
USA
USA
SU
[1,43]
H2O distillation
2026
1.8
Israel
[1.55]
D217O distillation
99.8
Germany
[1]
0.3
USA
[1.43]
2700-3500
40
USA
SU
[43]
17O
NO distillation at
low temp
16O
NO distillation at
low temp
99.99
99.9
[1]

65. •
•
•
•
•
Industrial Pilot Plant for the production of 18O
AIEA-Leipzig, 1977, Asatiani et al.
The growing demand for enriched 18O for scientific research with
labeled atoms poses a problem of industrial production. At the
present, the distillation of nitric oxide at low temperatures is the most
economical and effective separation method. This process has very
good prospects for industrial production of both 18O and 15N as a
consequence of the large isotope shift in the vapor pressure
associated with these isotopes.
The plant consists of a profiled stepped cascade formed of terraced
separation columns with a total length of 40 m. The plant has a
condenser, and the cascade steps are connected by intermediate
evaporators. Distillation is performed at a pressure a little above
atmospheric.
The plant produces several kg/year of 18O at an enrichment of 90 95 at %. At the same time it allows the production of NO enriched
with 15N.

66. Production of 17,18O by countercurrent distillation of
reactor-grade heavy water
AIEA-Leipzig, 1977, D. Staschewski
•
•
•
•
Heavy water produced by electrolysis and distillation is a unique source for the extraction
of heavy oxygen isotopes. The pre-enrichment of these isotopes in reactor grade D 2O
(enriched up to 1.4 at % 18O and 0.12 at % 17O by Norsk Hydro) was directly utilized in the
Karlsruhe separation plant, consisting of 4 distillation units with a total of 44 columns. The
steam-heated columns, mostly 12 m high, and 100, 34 or 12 mm in diameter contained the
well-known packing of oxidized phosphor bronze wire gauze. The pre-stage units yield
products enriched up to 20 at. % 18O and 1 at. % 17O which was fed to an intermediate
cascade where the final upgrading of 18O toward absolute isotopic purity and enrichment of
17
O to a level of 10 at. % take place. Unlike these units the distillation facility for high
concentrated 17O was run with H2O as the holdup. Consequently the intermediately product
enriched in 17O (- D217O) was converted electrolytical into H 217O. Electrolysis cells are also
used to produce chemical pure 18O2 gas from D218O for various syntheses.
The Karlsruhe separation process was a countercurrent distillation of heavy water at an
average temperature of 74 oC and a pressure of 200 torr at the top of each column.
The considerable delay in the columns in water distillation places a serious limit upon the
speed of isotope enrichment. To produce high-grade 17O with a reasonable time, the input
of isotopes has to be increased by a more efficient basic unit. For this purpose a new
basic cascade consisting in an arrangement of 16 columns, consuming daily a total of
4000 kg of steam has been take into consideration. A continuous feed flow of 800 liters of
D2O yearly would yield a bulk isotope transport of 11 kg of 18O and 0.7 kg of 17O which are
obtained as separate products. The intermediate product enriched to 4 at. % 17O is to be fed
immediately to the present main cascade, where a second intermediate product enriched
to 40 at. % 17O would be available in steady-state operation which could be upgraded, after
conversion, to very high enrichment in the H 2O distillation unit.

67. Osiashvili E.D. et al: Production of O-18 labeled water
… Leipzig TC-90, 1977.
•
•
O isotopes have a wide applications in the various fields of science
and technology. The distillation of nitric oxide at low temperatures is
the most effective and widespread method for separating oxygen
isotopes. In this case nitric oxide is enriched simultaneously with the
important oxygen and nitrogen isotopes.
However, oxygen isotopes in the form of nitric oxide have no
practical application. For scientific research and for solving some
tasks in modern technology , oxygen isotopes in the form of water
are required. Water with changed isotope content is also an initial
substance for the synthesis of many compounds labeled with
oxygen isotopes. In this purpose the reduction of nitric oxide with
hydrogen in the presence of various catalysts ( cobalt, nickel,
platinum) is performed.

68. D. Halliday et al. – The Use of SI in Medicinal
Chemistry, (1978)
•
•
•
•
O was first produced commercially at the Weizmann Institute in Israel from the
distillation of water [54] and this method has subsequently been developed in
combination with thermal diffusion to have a capability of producing 18O at 99.9 atom%
and 17O at 96 at.% [55].
At the Nuclear Research Centre at Karlsruhe (Germany) 18,17O was separated by
distillation of heavy water. This work was carried out in collaboration with NorskHydro, capitalizes on the fact that there was enrichment of heavy oxygen isotopes in
the Norwegian manufacture of heavy water [23]. In this plant, the feature of which has
been described [56], 18O was produced at 99.9 at.%. Intermediate product was
converted into H2O and fed to a distillation unit in order to produce useful enrichments
of 17O (approaching 30 at. %). Water-16O (depleted in both 17O and 18O) was produced at
99.99 at. % 16O.
The separation of 16,17,18O by cryogenic distillation of nitric oxide was used at Los
Alamos (USA).
Cryogenic distillation of oxygen is an effective method of producing 18O economically
at lower enrichments (25 at. %). The method is limited by the fact that 16Oin the
feedstock is present as 16,18O. By randomization of the molecular species, for example
by heating, higher enrichments could be attained [26]. The technique provides a
ready source of depleted material (16O2).
18

69. Leipzig 1977
•
•
Many interesting developments are to be expected in the
applications of stable isotopes of oxygen, particularly 18O. For this
purpose is necessary the increasing availability of this isotope at
lower cost. Fortunately, for many applications in the life sciences, it
is not necessary to use very pure 18O. Enrichment to 90 % or even
75 % is high enough in most cases. When using 18O, however, care
has to be taken because of the tendency of this isotope to undergo
exchange reactions. Activation analysis seems to be a very
promising method for the determination of this isotope.
18
O also has important applications in connection with the study of
cells and tissues by NMR methods, e.g. for the investigation of the
nature of water in normal and cancerous cells.

70. J.G. Tracy et al. – SI Enrichment Techniques and ORNL
…,1987
• Introduction
• A broad spectrum of enriched SI is needed for basic and
applied needs. Isotopes of prime importance, isotopicpurity requirements, and quantities of material are
continually changing, and the timely availability of highlyenriched materials are the subject of concern. Many of
these isotopes are crucial to the continuation of research
investigation and directly impact the nation’s health-care
delivery programs.
• The purpose of this paper is to review the current isotope
separation program and presents state-of-arts
techniques utilized to achieve specific isotope
requirements.

71. Producers, methods, capacity
ICON (Los Alamos National Laboratories, USA):
NO distillation -------------------------- 13 kg/y
CIL (Cambridge Isotope Laboratories, Xenia, Ohio, USA):
Water distillation ---------------------- 250 kg/y
Rotem Industries (Israel):
Water distillation ----------------------250 kg/y
Marshall Isotopes (Israel):
Water distillation ------------------ 100 kg/y
Isotec (USA): NO distillation, CO distillation(?) --- ?
Isonics (Russia ?) ------------------------------ ?
ISI (Georgia, Tbilisi) NO distillation ----- 30 kg/y
(Ukraina, Russia, Canada? …) ------------ ?
Isoflex (Russia) Isotopes, incl. 18O)

72. Conceptual TD Cascade
for Enrichment Oxygen-17
C3
W1
B
C4
C2
P1
F
C1
A
See explanations in text !
C5
P2
C6
W2

73. Production of stable isotopes by membrane method
Separation of Water Isotopomers by Porous Hydrophobic Membrane
(Institute of Nuclear Chemistry and Technology, Warsaw, Poland)
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Water enriched with its natural isotopes plays an important role in research and technology.
Heavy water (HDO, D2O) is used in nuclear technology and research and the increasing
market demand is expected in future if nuclear fusion will be used for energy production.
Water enriched in 18O is used in research and medicine in trace experiments, as is
water enriched in 17O. Recently there appears to be significant market demand for increased
production of heavy oxygen (18O). Its role is becoming more important as large amounts of
heavy oxygen is used for production of 18F for PET scanning.
The method of separation of water isotopomers proposed in the project is thermal
evaporation through a porous hydrophobic membrane (membrane distillation). The unit
separation factor for the process was determined in experiments carried out with a laboratory
apparatus, equipped with PTFE flat sheet membranes. The experiments showed the membrane
process is characterized by higher separation factors than distillation of water. Since
distillation is now the only commercial method for heavy oxygen production the proposed
process has particular importance. In some cases the method can be also applied for a
production of heavy water. Preliminary engineering calculations based on cascade theory
showed many advantages of membrane permeation. Employing the system of two countercurrent
cascades combined in series results in savings in stage number, reflux ratio, and
energy demand. The technical and economic evaluation of permeation as compared to other
enrichment methods showed the competitiveness of membrane process. The process was
experimentally tested with different multistage systems.
The method can be applied for a separation of isotopes of hydrogen and oxygen in
natural water. It can be used separately or in combination with other separation processes.

74. Production of stable isotopes by membrane method
Production of heavy oxygen (18O)
(Institute of Nuclear Chemistry and Technology, Warsaw, Poland) 1
O is widely used in research of mechanisms of catalytic reactions. Double-labeled
water with 18O and D is employed in metabolism studies to measure energy expenditure and
the total body water composition in human subjects especially when subjected to extreme
conditions, e.g. during surgical operations, persons under treat, etc. To increase precision of
measurements triple-labeling is sometimes employed ( 18O, 17O and D). In contrast to other
oxygen isotopes 17O possesses a magnetic moment, which allows easy detection using NMR.
Over the past few years the world has witnessed a continuously increasing demand for
enriched oxygen isotopes, especially 18O, due to a large consumption of H 218O by positron
emission tomography (PET, a new medical diagnostic technique used principally for tumor
detection). PET uses short-lived positron emitters, like 11C, 13N, 15O and 18F incorporated into
bio-chemically active tracer molecules absorbed preferentially by the tumor. The subsequent
radioactive decay monitored by sophisticated position sensitive detectors permits to tumor
or target organ to be mapped at high resolution
18

75. Production of stable isotopes by membrane method
Production of heavy oxygen (18O)
(Institute of Nuclear Chemistry and Technology, Warsaw, Poland) 2
•
Several different target materials are used for a production of these isotopes (Table 1), among
them water enriched in 18O.
Nuclide
C
13
N
15
O
18
F
11
Table 1. TARGET SYSTEM
Half-period [min]
Reaction
14
20.4
N (p, a) 11C
16
9.97
O (p, a) 13N
15
2.07
N (p n) 15O
18
109.8
O (p, n) 18F
Target material
Nitrogen gas (natural)
Water (natural)
Nitrogen gas (15N - enriched)
Water (18O – enriched)
Heavy oxygen water (H218O) is used as a target material for production of the short lived
radioisotope 18F used in PET scanning. 18F is obtained efficiently using the
nuclear reaction: 18O (p, n) 18F, induced in small PET cyclotrons (~11 MEV). As 18F and the
other product isotopes in Table 1 are short-lived, the cyclotrons are installed directly in
hospitals or clinics. A typical tomography centre comprises specialized cyclotron for short lived
positron isotope production, a laboratory for the synthesis of labelled tumor-specific
compounds, and a positron tomograph.

76. Fig.1. Laboratory stand for isotope separation experiments
In the 1990’s at Institute of Nuclear Chemistry and
Technology, Warshaw, the new method of
heavy oxygen enrichment in natural water was
elaborated. The method based on permeation
through porous, hydrophobic membrane, called
membrane distillation produces higher
separation factors than distillation of water. Unit
separation factors in membrane process were
determined in the experiments carried out with a
simple laboratory apparatus equipped with
flat sheet PTFE membrane (Fig.1).

77. Note
• The experiments showed the separation factors
of membrane permeation process are markedly
higher than those obtained for distillation of
water.
• Since the distillation is the main process used
for heavy oxygen enrichment the membrane
process is of particular importance.
• Preliminary engineering calculations based on
the separation cascade theory showed the
advantages of membrane permeation.

78. Fig.2. Double system of separation cascades for isotopes enrichment
•
•
•
The application of double system
of counter-current cascades
connected in series (Fig.2)
resulted in reduction of number of
stages, reflux ratio, energy
consumption.
Technological and economical
evaluation of permeation in
comparison with other methods
used for oxygen isotope
enrichment showed the
competitiveness of membrane
process.
The method proposed in patents
[1-5] can be used separately or in
combination with other separation
processes.

79. Table 2. Comparison of heavy oxygen enrichment methods
The methods of heavy oxygen enrichment are very expensive and very often difficult
in their technological accomplishment. Effective processes as thermodiffusion or chemical
isotope exchange are characterised by low kinetics. NO distillation exhibits a large separation
factor (Table 2), however it is disadvantageous because of high price of feed material, its
toxicity, difficulty with handling and inconveniently low process temperatures.
Table 2. Comparison of heavy oxygen enrichment methods
Process
Unit separation factor
Energy consumption
per 1 kg H218O [GJ]
Apparatus
Industrial hazard
Water
Distillation
1,0032
4-8
Simple
Normal carbon steel
Safe
Water
Permeation
1,005-1,04
1 - 12
Simple
Normal carbon steel,
plastics
Safe
NO
Distillation
1,0406
-
Complicated,
special materials,
corrosion hazard
NO – toxic
substance

80. Patents
•
•
•
•
•
- A. G. Chmielewski, G. Zakrzewska-Trznadel, N. Miljević, W.A. Van
Hook, Sposób wzbogacania wody w składniki wody cięŜkiej,
PL161104 (31.05.1993).
- A. G. Chmielewski, G. Zakrzewska-Trznadel, N. Miljević, W.A. Van
Hook, Sposób wzbogacania wody naturalnej w tlen-18, PL 16 1105
(17.05.1994).
- W. A. Van Hook, A. G. Chmielewski, G. Zakrzewska-Trznadel, N.
Miljević, Enrichment of Water in Components of Heavy Water,
U.S.Patent 5,084,181, (Jan. 28, 1992).
- W. A. Van Hook, A. G. Chmielewski, G. Zakrzewska-Trznadel, N.
Miljević, Method of Enrichment of Oxygen-18 in Natural Water, U.S.
Patent No 5, 057, 225 (Oct. 15, 1991).
- G. Chmielewski, G. Zakrzewska-Trznadel, N. Miljević, W.A. Van
Hook, Sposób wzbogacania wody naturalnej w tlen-18, PL 168 152
(09.08.1995).

81. SILEX technology
•
18
•
18
O is used in several different fields, including scientific research,
geology and medical imaging. By far the biggest demand for 18O is
for PET medical imaging. The market for this application is currently
approaching US $ 100 m and is rapidly growing.
O is currently produced via old and ineffecient distillation
techniques. The potential for highly effecient production with SILEX
technology could result in significant economic value for the
compant.

82. SILEX – Australia
26 February 2004
Stable Isotope Program,
with the primary focus on silicon and oxygen enrichment.
•
The design and construction of a prototype oxygen enrichment facility include
a laser system, photo-reactor vessel and associated gas handling system.
•
The prototype facility under construction in 2004, enrichment tests will be
conducted in the first half of 2005.
•
This facility could then be potentially modified to produce initial commercial
quantities of the 18O isotope used primarily in PET medical imaging.
•
The world market for oxygen 18 is currently estimated to be worth
approximately US$50M p.a (not including demand for milit. LIDAR appl.)
laser system

83. METHOD OF CONCENTRATING OXYGEN 18 WITH LASER
Japanese Patent 1991
• A method of concentrating 18O with laser which
comprises adding optionally a hydrocarbon to a
saturated acyclic ether (except dimethyl ether) or
a saturated cyclic ether as a starting material
containing 18O and laser beams are applied
thereto for causing selective photolysis of 18O,
and separating a product containing 18O from the
products of said photolysis. The concentrated 18O
can be used as a tracer or the like.

84. PHOTOCHEMICAL SEPARATION OF ISOTOPES
CA Patent 1122567 by Andreas Ch. Vikis
• A method for photochemical separation or enrichment of
isotopes of 13C and 18O employing 123.58 nm resonance
radiation of Kr of selected band-width and degrees of
self-absorption in order to excite selectively to the AlII v'
= 13 state, 13C16O, 12C18O, or both 13C16O and 12C18O
simultaneously,in a mixture of isotopic CO molecules
where the 12C16O isotopic molecule is in a large excess.
The electronically excited isotopic CO molecules react
with a second reactant to yield isotope enriched final
products which can be separated; for example, ground
state CO as second reactant yields CO2 and C3O2
products.

85. Production of stable isotopes in RRC “Kurchatov Institute”
Location of main producers of stable isotopes in Russia:
ECP, Zelenogorsk
SCP, Seversk
UCP, Novouralsk
EChPr, Lesnoi, EM
ECP, Nizhniy Novgorod
Sarov
Moscow, RRC “Kurchatov Institute”
ECP, St.Petersburg
ELP, Angarsk

86. American Elements
• American Elements is a manufacturer and supplier
specializing in the Stable (non-radioactive) Isoptopes of
numerous elements and their oxide and fluoride
compounds marketed under the trademark AE
Isotopes™, including Oxygen (18O)
• Isotopes from American Elements are non-radioactive
materials with numerous applications and properties.
• 18O has been used extensively to study human
metabolism by measuring metabolic energy output in
research involving obesity, heart disease, osteoporosis
and diabetes. 18O can be traced through the body using
mass spectrometry.

87. Applications
•
H2O of 95 % 18O  Positron Emission Tomography (PET)
18
O  18F
Production:
35 kg/an in 1997
600 – 1000 kg/an in 2004
of 120 – 200 mil. USD/year
•
D2O of 10 at-% 18O  Organisms energetic consumption
studies
•
Others applications (labelled compounds, 17O in RMN imaging,
etc. )

88. Research Projects - A.E. Ruggles
RESEARCH PERFORMED AT THE UNIVERSITY OF TENNESSEE
Title: Fluorine 18 Target Optimization 2001-2003, CTI, inc.
• Isotope production for Positron Emission Tomography
(PET) is currently accomplished using cyclotrons
producing 11 MeV protons. The protons bombard targets
with 18O feedstock to produce 18F. Water enriched with 18O
is a favorite target material. The short half-life of the 18F
encourages rapid production and distribution cycles. The
expense of the 18O motivates high conversion rates and
small target inventories. The research focused on
maximizing the beam power deposited per unit target
mass while maintaining pressures and temperatures at
levels acceptable to conventional beam window
materials.

89. V.L.Avona et al. – Improvement of human condition by
the use of SI, 1990
•
•
SI find a myriad of applications which directly or indirectly improve
the quality of human life or aid in the study of how to preserve our
natural resources. Some of the most notable uses of SI are in the
fields of agronomy, marine biology, environmental science, nutrition,
biochemical research, medical diagnostics and medical therapy.
The intent of this section of the paper is not to give detailed
coverage of the many applications of SI. It does however present an
overview of the recent research with stable isotopes of oxygen
which will ultimately benefit humankind.
Stable isotopic-labeled compounds offer several advantages over
radioactive tracers. First, some biologically important element, e.g.
oxygen, have no radioisotopes with sufficiently long half-lives to
allow their practical use in biological systems. Secondly, several
different isotopomers may be used simultaneously in a single study.

90. 1. V.L.Avona et al. – Improvement of human
condition by the use of SI, 1990
• Conclusion: SI of oxygen have a wide
range of applications in almost every
natural and physical science. The purpose
of this brief review was to describe a few
important applications to illustrate the
possible uses for enriched stable isotopes
of oxygen.

91. R. DeWitt – Enriched Isotope Applications:
Biomedical Field, 1979 (ICON)
•
•
•
•
•
•
•
•
•
•
Enriched isotope applications in the biomedical field could require isotopes in gram to kilogram
quantities. For the stable isotopes now available in large quantity at reasonable cost, such as the
isotopes of oxygen, large clinical applications are either in the process of being established or are
in the development stage.
The recent proliferation of particle accelerators in hospitals, universities, and radiopharmaceutical
firms, along with widespread acceptance of the clinical use of accelerator-produced
radionuclides, can greatly accelerate the increased need from gram to kilogram quantities of
enriched stable isotopes of oxygen.
Note: By definition, a stable isotope is one with very long half-life (greater than 10 10 yr). That
stable isotopes are often used as feed material (enriched isotope targets) to prepare radioactive
isotopes by nuclear transmutation.
Oxygen isotopes are found in varying amounts in human body, the amount of which depends in
general, upon their concentrations in local soli, food, and atmosphere. They are of interest
because of their essential role in the life process.
Principal methods of separation of oxygen isotopes in current use (1979):
16
O – Distillation NO, H2O at 99.98 – 99.99 at.% ; 1000s kg/yr
17
O - Distillation NO, H2O at 20 – 40 at.%; 2 -5 kg/yr
- Thermal Diffusion O2 at 96 at.%; 0.01 kg/yr
18
O - Distillation NO, H2O, D2O at 90 – 99.99 at.%; 0.2 – 0.4 kg/yr
At LANL large quantities of ICON’s are produced by low temperature distillation of carbon
monoxide and nitric oxide.

92. PET scanners have a cyclotron
(particle accelerator) in which 18O is
converted in Fluorine-18 (18F), which
is bonded to sugar molecules and
injected into a patient's bloodstream.
18
F is radioactive, with a two-hour halflife. It is absorbed by body tissues,
coloring diseased areas.

93. ISI, Tbilisi, Georgia
January 18, 2004
at NO distillation plant – two dead

94. Separation methods of O-18 taken into
consideration
NO cryogenic distillation
Thermal diffusion
Water distillation
explosion peril
no feasible

95. Appendix
•
•
•
•
•
•
•
•
H.G. Spicer – Methods for separating SI, Isotec, 1990.
General considerations
Enriched SI of many elements are widely used in agriculture, medicine, chemical processing,
scientific research and in a variety of specialized industrial processes.
This paper reviews the various industrial methods used to separate stable isotopes of oxygen.
The separation processes are considered from a commercial viewpoint. The separation
technologies presented include distillation, thermal diffusion, chemical exchange, ion exchange ?,
…The comparative advantages and disadvantages of these methods are discussed. Additionally,
a table is given that summarizes most methods that have been investigated or used in oxygen
isotopes separation.
A stable isotope of an element is an isotope that is non radioactive or has a half-life exceeding
5x108 years. There are 63 elements having multiple stable isotopes. These elements gives us
more than 260 total isotopes to separate.
In the case of oxygen, current production methods are Distillation (DIST) and Gaseous Thermal
Diffusion (GTD) and in R & D area, MLIS (Molecular Laser Isotope Separation), IEX (Ion
Exchange) and CHEX (Chemical Exchange)
Distillation (DIST) is an economical technique for separation of many light isotopes. Industrially
distillation is used to separate the isotopes of oxygen.
Gas-phase thermal diffusion (GTD) is currently used for the separation of noble gas isotopes. TD
plants generally have low capital cost. TD is a versatile process for producing small quantities of
isotopes. The main disadvantage of this technology is that it has a high product unit costs due to
a small production rate per column and large electrical consumption. There is ni significant
economy of scale in TD plants.

96. •
•
Chemical exchange (CHEX) is used for separation of oxygen isotopes. Since
chemical exchange processes use conventional chemical process equipment they
can be easily scaled. The elementary separation factors are usually better than
distillation for the same isotope. Generally, chemical exchange processes have a
good economy of scale. However, the processes require expensive chemical
refluxing unless thermal or electro-chemical refluxing is possible. Often the systems
require the use of highly toxic and corrosive gases.
Molecular laser isotope separation (MLIS) is actually a group of related processes
utilizing laser induced photochemical reactions which can be made isotopic selective
by precise adjustment of the laser wavelength. Potential MLIS processes have been
discovered for the isotopes of oxygen. LIS is achieved by irradiating one of the
isotopic components (usually the rare one) so that it is selectively excited. The
excitation then drives this particular isotope to react and form products that are
enriched in it. MLIS research has demonstrated isotope separation factors higher
than 8000 for one step. Also laser technology has been steadily improving output
power while the cost/kW has been decreasing. This situation indicates a promising
future for this type of process. Two significant problems with many MLIS schemes is
that the feed materials are often expensive compare to feeds used in other processes
and that the reaction products often requires expensive chemical conversions to
arrive at desired product form.