Revisiting Low Energy Deuteron Production of [18F]
Fluoride and Fluorine for PET
T. E. Barnhart1, R. J. Nickles1 and A. D. Roberts1,2
1
Medical Physics and 2Psychiatry Departments,
University of Wisconsin, Madison, Wisconsin
1500 North Highland Ave., Waisman Center, Madison, WI, USA 53705
Abstract. Fluorine-18 is currently the most widely used radioisotope in PET imaging. While much attention has been
paid in recent years to production methods from 18O(p,n)18F, the current work revisits production techniques using nonenriched neon targets and the 20Ne(d,α)18F reaction. While this reaction was originally pursued, and ultimately replaced
by the higher yielding 18O reactions, there is an opportunity using high current low-energy deuteron accelerators and the
inherent simplicity of gas targetry to provide viable alternatives to the costly 18O water target systems. 18F production
systems have been developed for the gas-phase 20Ne(d,α)18F reaction with deuterons from a 3MV NEC 9SDH-2
electrostatic tandem accelerator. High power target systems allowing for irradiation in excess of 100uA provided [18F]F2
yields to 86% of the theoretical maximum, and [18F]F- yields with a wash-off system of 80% of the maximum.
While targetry using the 20Ne reaction is unlikely to
replace higher yields of the 18O reaction, it does still
have practical utility and some advantages. The target
material is not isotopically enriched, inexpensive, and
does not have to be recollected. Gas targets also
permit higher beam currents, thereby allowing
production of substantial yields in neon targets.
INTRODUCTION
The production of [18F] fluoride and fluorine has
been studied extensively due to its importance in the
PET imaging community. Production techniques from
the 20Ne(d,α)18F reaction have been described by many
groups for [18F]F- (e.g. Blessing et al.[1],Helus et al.,
[2]) and for [18F]F2 (e.g. Bida et al.[3], Casella et
al.[4], Wieland et al.[5,;Blessing et al.[1], ) With the
development of 18O targets utilizing the higher
yielding 18O(p,n)18F reaction, larger quantities of 18F
are produced. [18F]F- is generally produced from 18OH2O(e.g. Wieland et al.[6], Bergman et al. [7],
Kilbourn et al. [8] , Roberts et al. [9], Ohlsson et al.
[10] ,) and [18F]F2 from 18O-O2 gas ( Nickles et al.
[11], Chirakal et al. [12], Roberts et al. [13], Bishop et
al. [14], Bergman and Solin [15]). Several groups
have investigated the use of 18O-O2 for fluoride
production, taking advantage of the simplicity and
high performance of gas targetry then washing off
[18F] fluoride in water(e.g Nickles et al.[16] and Ruth
et al. [17]). Of particular interest was the investigation
of suitable materials for wash-off targetry [2].
Niobium has been proposed as an ideal material for
minimizing [18F]F- loss [18].
The current work presented here explores the
potential and practicality for 18F production with high
current, low energy deuteron accelerators.
In
particular, we investigated feasibility of high-yield 18F
wash-off targetry using niobium.
MATERIALS AND METHODS
Accelerator
The National Electrostatics Corporation 9SDH-2
Pelletron was conservatively designed for 100 µA of 6
MeV protons or deuterons in a 10 mm beamstrike.
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
1086
The actual performance regularly exceeds these
specifications with accelerated beam currents on target
in excess of 115 µA. This is in part due to the Torvis
multi-cusp ion source [19], typically achieving more
than 150 µA. The dome voltage of 2.97 MV required
for 6 MeV single charge beams (with a 50 keV ion
source voltage) has been run up to 3.67 MV (for 7.4
MeV beam). The beam tuning components include
low energy steering, and high energy quad focusing
and steering magnets. Beam tune is monitored to
maximum beam current with an in-line rotating wire
beam profile monitor (NEC model BPM-80) allowing
for fine, continuous control of the beam shape and
position in two dimensions with negligible losses.
FIGURE 1. Typical gas target assembly. (A) is the gas
target body with 19 mm I.D and 127 mm length bore, (B) is
an 020 Viton O-ring, (C) is the entrance foil, (D) is and an
024 Viton O-ring, and (E) is the water-cooled support grid.
Improving the total yields of 18F produced by a low
energy linear accelerator (the NEC 9SDH-2 3 MV
electrostatic tandem) required the improvement in thin
entrance windows isolating the target gases from the
vacuum. A high transmission grid (70% transmission)
allows for beam current in excess of 100 µA protons
or deuterons required for high-activity 18F production
[20]. Another advantage is small hole diameter with
coupled grid cooling increasing the burst strength.
This allows for the use of thinner windows with an
associated reduction in energy loss versus a double foil
helium cooled window.
Gas Targets
Flow-through gas target systems are used on the
NEC accelerator for the production of [18F] F2 and
[18F] F-. Figure 1 shows a typical example of gas
target layout and dimensions. Mixed target gasses
feed the target via 1/16” O.D. stainless tube with a
short PTFE section for electrical isolation. The gas
enters the target at the downstream end though a
stainless steel 1/16-NPT fitting, and exits through a
1/16-NPT fitting within 1 cm of the upstream end.
The radioactive gas is then delivered to the analysis
station though 30 m of HPLC grade 0.8 mm I.D.
stainless steel tube or 0.8 mm I.D. PTFE tube, at a rate
of up to 300 ml/min. The target pressure is monitored
with a corrosion resistant capacitance manometer
(Entran Devices, Inc. 10 Washington Ave., Fairfield,
NJ 07004-3877, USA) mounted on the gas line near
the target feed. The target pressure is controlled by the
gas flow, supply pressure, and the impedance set by a
needle valve on the end of the target. A typical watercooled target body is 6061-T1 aluminum with a
cylindrical bore 12.7 cm long by 1.9 cm I. D. To
facilitate the washing of the fluoride from the target
wall, the wash-off target has been nickel plated and
lined with a niobium tube (.75” O.D., .67” I.D.) Gas
pressures of the targets used on the 9SDH-2
accelerator typically operate at 100-150 psi under
constant flow conditions with pressure maintained by
the gas cylinder regulator. The targets are mounted to
the support grid with the thin entrance window foil of
10.2 to 12.7 µm Havar or 25.4 µm aluminum
compressed between Viton o-rings. Beam profiles for
irradiating on the standard large bore gas targets are
typically held from 8 to 10 mm FWHM.
The window support grid consisted of circular
holes arranged in a hexagonal pattern [20]. Figure 1
shows the basic design of this grid constructed as a
single aluminum unit, incorporating water-cooling for
improved heat transfer The deep grid holes provide
increased material for heat transfer to the watercooling with negligible loss of the near parallel beam
current. Circular holes were made with 1.7 mm
diameter with walls 0.18 mm thick between the holes.
The grids are water cooled via two straight channels
on opposite sides of the grid. Chilled water at 18 C
flows at 2.3 l/min through the cooling channels.
The water wash system for [18F] fluoride
production in figure 2 is used for both supplying the
neon gas to the target and for washing the fluoride
from the walls of the target. All valves consist of
Swagelok 1/16” stainless steel 3-way valves (SS41XS1) except for the 1/16” Swagelok needle valve
(SS-SS1). The vessels are 25 cm3 double-ended
stainless steel sample cylinders (SS-4CD-TW-25), also
from Swagelok. All tubing in the setup is 1/16”
stainless tubing except for the short PTFE section on
the target for electrical isolation. Surface preparation
of the water wash system includes several rinses with
HPLC grade water and drying with the neon target
gas.
Under irradiation conditions, valve 1 is open to
the neon supply tank and to the target. Valve 2 is open
to valve 3 and out through the needle valve. To wash
the target, valves 1 and 3 are open to vent and the
1087
18.7 mCi/µA (corrected for 70% transmission through
the grid) which is 81.% of the theoretical maximum.
The 6.5 MeV beam (6.09 MeV on target) saturation
yields averaged 22 mCi/µA (transmission corrected),
which is 76% of the maximum theoretical yield. At
6.9 MeV (6.5 on target) the saturation yield was
measured to be 30.5 mCi/µA (transmission corrected),
86.7% of the maximum theoretical yield.
target is depressurized. Hot water (~80°C) is then
loaded through valve 1, after which valve 2 is closed.
Valve 1 is then opened to the neon, pressurizing the
system thereby forcing the water out of the first vessel,
filling the target completely and overflowing into
vessel 2. When the water has completely left the first
vessel, the neon pressure is turned off on valve 1 and it
is vented to atmosphere. After venting, valve 1 is
closed, and valve 2 is opened to the neon, forcing the
water back into vessel 1. The washes are repeated at
least three times. To unload the target, valve 4 is
opened where the water can be collected or pushed
through a trap and release column. Pressure is applied
to the side of the system containing the water, through
valve 1 or 2, until only gas comes from the target.
Last, that valve (valve 1 or 2) is closed and the other
side is pressured (valve 1 or 2) to purge any remaining
water in the vessel and lines.
35
Yield (mCi/µA)
30
25
20
15
5.5 MeV
6.0 MeV
6.5 MeV
10
5
0
10
30
50
70
90
Beam current(µA)
Figure 3. [18F] F2 saturation yields vs. beam current and
deuteron energy
To accommodate the production of [18F]-DOPA,
higher specific activity is required. A two shot method
was employed with only neon in the first irradiation.
During the second irradiation, the He/F2 gas flow set to
3 µmol of F2/min for 30 minutes for a maximum
amount of F2 under 100 µmol. This gave a yield of 5.4
mCi/µA at 60 µA. Fluorine reactivity was confirmed
with successful synthesis of F-DOPA using standard
techniques.
Further trials will be performed,
optimizing the amount of carrier F2 and time required
to remove the [18F]F2 from the target with sufficiently
high specific activity so that the is useful as a
precursor.
Figure 2. Schematic of the fluoride wash-off system
20
Removal of the [18F]F- from the niobium tube lined
gas target was optimized though several trials.
Initially, to test the efficiency of release of the [18F]Ffrom the walls, the target chamber was opened and
manually rinsed by pouring hot (80°C) water into the
target entrance. This gave 86% of the total activity in
the first rinse and 4% in the second rinse with 10% left
on the target.
RESULTS AND DISCUSSION
20
Ne(d,α)18F, for Aqueous [18F]Fluoride
Ne(d,α)18F, for [18F]F2
[18F]F2 is produced via 20Ne(d,α)18F using a neon
gas mixed with up to 10% of a mixed gas of
helium/fluorine (95% He/5% F2). Saturation yield
measurements were done versus beam energy (6.0 to
6.9 MeV) and beam current (20 to 90 µA). The results
of these trials can be seen in figure 3. For the 6 MeV
beam (5.56 MeV on target) saturation yields averaged
The next method involved injecting 80°C directly
into the sealed target as it sits on the beam line.
Repeated single water washes of 20 ml averaged 33%
of theoretical maximum yield in the first wash, 15% in
1088
theoretical maximum, and [18F]F- yields with a washoff system of 80% of the maximum.
the second, 6.7 % in the third, down to .6% in the sixth
wash. These results can be seen in figure 4.
The final method employed the wash off setup in
figure 2. Thirty-five ml of 80°C water was injected
into the vessel where neon gas pressure pushed the
water back and forth through the target. The washing
was repeated in both directions approximately three
times. The purpose was to increase the mechanical
washing action of the flowing water and essentially
recirculating the same water the target, reducing the
total volume. Figure 4 shows the results of repeat
rinses using the wash-off rig. The first 35 ml rinse
averaged 62% of the theoretical yield, the second 14%,
and the third 3% totaling 80% of the theoretical yield.
The total activity recovered has been as much as 576
mCi. Fluoride reactivity was demonstrated with
successful FDG syntheses using the first 35 ml
recirculated water load.
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1.
2.
3.
4.
5.
6.
7.
% Theoretical Activity
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100
8.
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9.
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10.
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20
11.
Recirculated
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14.
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15.
16.
17.
CONCLUSION
18.
The current work provides production techniques
using non-enriched neon targets, though production
methods from the higher yielding 18O(p,n)18F reaction
will probably remain the industry standard, While this
20
Ne(d,α)18F reaction was originally pursued, and
ultimately replaced by 18O reactions, it is a viable
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Water-cooled support grids withstanding deuteron
irradiation in excess of 100µA increase production at
low energy. High power target systems have been
shown to provide [18F]F2 yields to 86% of the
19.
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