Experiments With Recirculating Target for F-18 Production
M.Y. Kiselev
Eastern Isotopes, Inc. Sterling, VA USA,
Abstract. Approximately 10 ml of O-18 water was loaded in an apparatus containing a 5 ml storage vessel, pump,
silver target attached to a cyclotron, filter, backpressure regulator, conductivity meter, several valves and ion exchange
cartridges. The water was continuously pumped through the target during proton bombardment at a rate 5 ml/min.
Continuous irradiation with beam current ranging from 10 to 50 uA was conducted while pressure, temperature and
conductivity were continuously monitored. The results indicate that recirculating of the target water can increase
production of F-18 in relation to consumed O-18 water material. It can also increase productivity by eliminating idle
periods for re-filling the target. A backpressure regulator can precisely control target pressure. This method also allows
for continuous monitoring of the target material temperature, pressure, conductivity and accumulated radioactivity.
Results of these observations provide important information about target performance and physical processes taking
place inside the target.
extremely high amounts of target material in an
environment of commercial production.
INTRODUCTION
In most conventional liquid target systems for 18Ffluoride production the target is typically loaded with
enriched 18O water by means of a syringe or a pump,
the water delivery system is then isolated from the
target by means of a valve and target is irradiated.
This can be described as a “static” target, meaning that
the same target material remains in the target through
the irradiation time.
SYSTEM DESCRIPTION
Described herein is the modified method of 18Ffluoride production using continuous recirculation of
18
O-enriched water through the target during
irradiation. Produced isotope is periodically extracted
from the target material and made available for
utilization without interrupting recirculation and
irradiation. Addition of deionising cartridges allows
returning the target material after extraction of the
isotope back into the target. This allows reusing the
same portion of enriched water to produce multiple
batches of 18F-fluoride thus making this process
practical and economical in an environment of
commercial production.
Static targets do have significant disadvantages
including control of pressure and purity of the target
material, providing adequate heat dissipation and other
problems.
It has been proposed 1,2,3 to produce 18F-fluoride
and other isotopes by recirculating water through the
target. The increase in target yields in recirculating
target in comparison with a static target was observed.
It was also reported that radiolytic gases produced in
recirculating target can be efficiently captured and 18O
can be recovered.
The system described below was tested on IBA
Cyclone 18/9 and GE PETtrace ™ cyclotrons
equipped with respectively IBA and GE targets. Target
volume was between 0.8 and 2.2 ml. No modifications
to the targets were necessary to use this system.
In published examples the “one time” extraction
method was used, when the entire volume of water
was emptied from the circulation loop to recover 18F
fluoride. This would have lead to consumption of
The targets were irradiated with beam current
ranging from 20 to 50 uA and produced isotope was
CP680, Application of Accelerators in Research and Industry: 17th Int'l. Conference, edited by J. L. Duggan and I. L. Morgan
© 2003 American Institute of Physics 0-7354-0149-7/03/$20.00
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extracted every 30-120 minutes. The recirculating
target system and the FDG synthesizer were controlled
by the same digital controller system equipped with a
PC based user interface.
Extraction
When desired amount of 18F-fluoride is produced, the
flow of target material is directed through the QMA
cartridge by switching valves (V1) and (V2) as shown
in Fig. 2.
Target water temperature, pressure and electrical
conductivity were monitored and recorded at 1 sec.
interval as well as radioactivity in the QMA (anion
exchange cartridge supplied by Waters) cartridge and
expansion vial.
To hot cell
QMA
V2
Condenser
18
F-FLUORIDE PRODUCTION
HPLC
Pump
QMA
KHCO3
Exp. Vial
Helium
V3
BPR
Delivery
SAX
18
Target
HPLC
Pump
SCX
Once 18F-fluoride is extracted it is necessary to
remove all enriched water from the QMA cartridge to
avoid loss of this material during the following steps.
This is accomplished by switching valve (V1)
allowing helium gas pressure to push 18O-enriched
water out of the QMA cartridge.
To hot cell
V1
SAX
QMA cartridge retains fluoride. Target water is
then passed through ion retardation cartridges (SAX)
and (SCX) in order to remove ionic contaminants from
the water. Thus purified and depleted of radioactive
isotope material is returned into the expansion vial.
Refer to Fig. 1 for schematic diagram of the
recirculating target system during irradiation step. The
valve V1 directs flow of water into the vial, which
serves as an expansion vessel. Direction of water flow
is indicated with arrows in the diagram.
Condenser
V1
FIGURE 2. Extraction Step
Irradiation
V2
V3
BPR
Target
The process of production and delivery in this
system can be described as a sequence of irradiation,
extraction and delivery steps. It should be noted that
irradiation of the target is not interrupted during
extraction, delivery and FDG synthesis.
Helium
SCX
F-Fluoride accumulated on QMA cartridge is
immediately removed by passing three 0.5 ml portions
of 20-40 mM solution of potassium carbonate or
hydrocarbonate in water. Valves (V2 and V3) direct
eluate into the receiving vial located inside the hot cell
as shown in Fig. 3.
KHCO3
Exp. Vial
FIGURE 1. Irradiation Step
Activity retained in QMA cartridge was
insignificant in comparison to that remaining in
circulating water. High background in the cyclotron
vault makes it difficult to measure residual activity.
Overall system efficiency can be estimated to be 80%
as compared with amount of F-18 produced when the
entire amount of target material is delivered to hot cell.
The target material is being pumped through the
target followed by a water-cooled condenser, 10
micron filter and backpressure regulator (BPR) which
is used to maintain constant pressure of 250 psig in the
target. Pressure transducer (not shown in the picture)
is connected to the tubing connecting the target with
the filter. High-pressure Rheodyne valves control
direction of water flow.
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recirculating through the target as in irradiation step.
Production of isotope is not interrupted at all times.
To hot cell
QMA
V2
Condenser
V3
BPR
V1
Target
HPLC
Pump
Helium
FDG PRODUCTION
SAX
SCX
In experiments described below 18F-Fluoride was
delivered into a hot cell with FDG synthesizer and
FDG synthesis was performed using modified
Hamacker4 method. Reactivity of isotope produced in
this system was similar to that produced in a
conventional “static” system when processed in a
similar processing module using identical reagents.
KHCO3
Exp. Vial
FIGURE 3. Delivery Step.
Table 1 summarizes results of three consecutive 2hour productions performed without interruption of
irradiation using the above-described system and GE
PETtrace cyclotron equipped with standard highpressure target. The system was loaded with 10 ml of
95% 18O-enriched water supplied by Marshall isotopes
and recircuilated using Waters Model 515 HPLC
pump at a rate of 10 ml/min. Irradiation time is given
from the start of beam or from the end of previous
extraction step.
To facilitate delivery of the isotope through 20-30
meter 1/16” OD delivery tubing helium gas pressure of
30-50 psig is applied at the end of this step to push the
liquid out of QMA cartridge into the hot cell which
takes 2-3 min. Complete removal of liquid from the
cartridge is also critical to minimize isotopic dilution
of enriched water during the following extraction step.
During delivery step 6-port valve (V1) is returned
in its original position and target material continues
Irradiation
Time (min)
120
120
120
TABLE 1. 18F-Fluoride and 18F-FDG production using recirculating target
18
18
F Activity
FDG Activity
F Yield
FDG Yield
Bam Current
(mCi)
(mCi)
(mCi/uA*hr)
(% at EOS)
(uA)
40
3874
2160
48
56
40
3813
2350
47
61
40
4000
2580
50
64
The production cycle starting with extraction and to
the end of FDG production was approximately 30 min.
Water consumption
Since the same controller controls both the target
system and the FDG synthesizer the process requires
minimum operator intervention. The entire production
cycle is fully automated from extraction of the isotope
from the target through delivery of the final product.
There was no detectable by visual observation
change in amount of enriched water in the expansion
vial after three production cycles.
Electrical
conductivity of target water has also remained
unchanged. It should be however noted that reliable
data on isotopic enrichment of water before and after
use is difficult to obtain. Based on an assumption that
QMA cartridge may retain as much as 50-100 mg of
liquid after being purged with helium it may be
expected that every extraction cycle will reduce water
enrichment by approximately 0.5-1% resulting in
necessity to replace the entire volume of water loaded
in the system after approximately 10 cycles to
maintain 85% or greater enrichment.
Cyclotron operation is also simplified due to the
fact that there is no need to interrupt irradiation for
target delivery. In an environment of commercial
production when multiple batches are produced in one
day this can help to increase equipment utilization by
as much as 5-10%.
Circulating target material allows monitoring its
temperature, conductivity, pressure and radioactivity.
Extensive monitoring and data collection can provide
critical information needed to predict failures and
increase system reliability.
With system capacity of 10 g of target material
replacement of the entire volume after every 10 cycles
would lead to an average consumption of 1 g per
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batch, which is lower than the volume used to fill the
target. As a result more isotope can be produced per
each gram of target material used (depleted).
Further improvements to system efficiency can be
made by optimizing extraction process, i.e. minimizing
sorbent amount in the cartridge which is the main
source of isotopic dilution of enriched water as well as
capturing radiolytic gases which may contain some of
18
O in oxygen gas form.
CONCLUSIONS
Recirculating 18O-enriched water through target is a
convenient and practical way for preparation of large
quantities of 18F-fluoride, which can be used to
produce 18F-FDG. This approach allows reducing
consumption of expensive target material and
increasing production of the isotope.
REFERENCES
1. Yves Jongen, Benoit Georges WTTC 3rd Workshop
Proceedings p 50, 1989
2. Iwata et all, Appl. Rad. Isot. V.38, No 11, p. 979-9843.
3. B.H. Mock and L.A. Corbin WTTC 9th Workshop
proceedings, In print (2002)
4. Hamacher K, Coenen H, Stocklin G. J. Nucl. Med. 27,
235 (1986)
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