Use of SF6 for the production of electrophilic 18F-fluorination reagents

Article abstract of DOI:10.1016/j.jfluchem.2017.10.010

Electrophilic ¹⁸F-fluorination is an important method for production of tracers for positron emission tomography. The most commonly employed ¹⁸F-fluorination reagents [¹⁸F]F₂, [¹⁸F]Selectfluor bis(tri

Full text of DOI:10.1016/j.jfluchem.2017.10.010

JournalofFluorineChemistry204(2017)90–97
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Use of SF6 for the production of electrophilic 18F-fluorination reagents
Anna Krzyczmonika, Thomas Kellera, Anna K. Kirjavainena, Salla Lahdenpohjaa,
⁎
Sarita Forsbacka,b, Olof Solina,b,c,
a
Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland
Department of Chemistry, University of Turku, Turku, Finland
Accelerator Laboratory, Åbo Akademi University, Turku, Finland
b
c
A R T I C L E I N F O
A B S T R A C T
Keywords:
Electrophilic 18F-fluorination is an important method for production of tracers for positron emission tomo-
graphy. The most commonly employed 18F-fluorination reagents [18F]F2, [18F]Selectfluor bis(triflate) and [18F]
NFSi allow for the synthetically simple and fast introduction of fluorine-18 into organic molecules, in particular
those containing electron rich aromatic rings. For the time being the best method for the production of [18F]F2
gas, the most common electrophilic reagent, is a post-target production which applies a high voltage electrical
discharge to promote the 19F/18F isotopic exchange between [18F]MeF and carrier F2 gas.
Electrophilic 18F-fluorination
[
18F]F2
PET
Radiochemistry
SF6
[
18F]Selectfluor bis(triflate)
The aim of this study was to develop a new method for the production of electrophilic 18F-fluorination
reagents which would avoid use of toxic and very reactive carrier F2 gas. In this study the use of SF6 as an
alternative to carrier F2 gas was tested. Experiments were carried out in two different matrix gases: Ne and Xe.
The electrophilic 18F-fluorination reagent produced was used for the labelling of two model compounds (6-[18F]
fluoro-L-DOPA and [18F]Selectfluor bis(triflate)) in order to prove its feasibility.
This proof-of-concept study showed that SF6 in Xe can be used in place of F2 for the production of electro-
philic [18F]F2 gas. When SF6 in Ne was used only trace amounts of [18F]F2 was observed.
1. Introduction
voltage electrical discharge to promote the 19F/18F isotopic exchange
has been a highly useful method for the production of [18F]F2 gas as the
Positron emission tomography (PET) is a diagnostic technique
which allows the imaging of biological processes in living organisms.
This imaging modality visualises the distribution of radioactivity from
biologically active molecules that have been labelled with a positron
emitting radionuclide. Due to its numerous favourable characteristics
such as the clean β+ decay (97%), low positron energy (Eβmax = 635
molar activity (Am) is significantly higher when compared to Am’s
achieved by the in-target methods. This post-target approach starts
from the conversion of cyclotron-produced [18F]fluoride to [18F]MeF
through reaction with MeI. Next, the [18F]MeF, purified by gas chro-
matography, is mixed with a low amount of non-radioactive carrier F2
gas in neon in a quartz discharge chamber and atomized by a high
voltage electrical discharge. The [18F]F2 formed is bubbled through a
solution of labelling precursor without any further purification. This
technique has been used for the production of different PET tracers in
Turku PET Centre for more than twenty years [7].
In order to avoid the use of highly reactive and toxic F2 gas in the
production of [18F]F2, we decided to replace it with a milder gaseous
source of F2. It is known that SF6 can be dissociated by an electrical
discharge or plasma to create F2 as well as different S-F species [8,9].
This suggests that SF6 can be used as an alternative to F2 in the dis-
charge-promoted production of [18F]F2. Due to its inert and nontoxic
nature, SF6 is safe to use in the laboratory, moreover, the high density
(6.17 g/L) of SF6 makes it easy to dose the necessary small portions of
gas.
keV) and convenient half-life (t = 109.8 min), fluorine-18 is the most
½
commonly used of all the radionuclides that are suitable for the pro-
duction of PET tracers.
Nucleophilic 18F-fluorination is the most frequently employed ap-
proach for the introduction of fluorine-18 into organic molecules. The
complementary electrophilic 18F-fluorination route is an important
method for the production of PET tracers since it allows access to
molecules that are difficult to reach by the nucleophilic approach.
[
18F]F2, the simplest electrophilic fluorination reagent, can be
produced in-target by a cyclotron through the 20Ne(d,α)18F [1,2] or 18
O
(p,n)18F [3,4] nuclear reactions carried out on gas targets, or by post-
target production methods from aqueous [18F]fluoride [5,6]. Since its
publication by Bergman and Solin in 1997 [6], the application of a high
⁎
Corresponding author at: Turku PET, University of Turku, Kiinamyllynkatu 4−8, FI−20520 Turku, Finland.
E-mail address: olof.solin@abo.fi (O. Solin).
http://dx.doi.org/10.1016/j.jfluchem.2017.10.010
Received 11 September 2017; Received in revised form 24 October 2017; Accepted 24 October 2017
Availableonline31October2017
0022-1139/©2017ElsevierB.V.Allrightsreserved.

A. Krzyczmonik et al.
JournalofFluorineChemistry204(2017)90–97
Fig. 1. Syntheses of 6-[18F]fluoro-L-DOPA, [18F]Selectfluor bis(triflate) and [18F]F-DPA.
This research focuses on the use of SF6 gas for the synthesis of
electrophilic 18F-fluorination reagents. Presented herein are the result
for the reaction carried out in two different matrices; Ne and Xe.
The use of Xe as the matrix gas can potentially promote the pro-
duction of [18F]XeF2 [10,11] which is also an electrophilic 18F-fluor-
ination reagent [12–16]. It is relatively stable in solvents such as
acetonitrile (MeCN), dichloromethane (DCM) or trichloro-
fluoromethane (Freon-11) [17] and can be used for the production of
PET tracers.
fluoro-L-DOPA were successfully synthesised when 1% SF6 in Xe was
used as the source of carrier fluorine for the reaction (Fig. 2A). The high
voltage electrical discharge (32–36 kV) was applied to the SF6/Xe/[18F]
MeF gas mixture in a quartz chamber for 10, 50, 100 or 150 s. The
resulting gas mixture containing electrophilic 18F-fluorination species
was immediately used for the synthesis of 6-[18F]fluoro-L-DOPA. For
discharges of 50–150 s, the tracer was produced with good radio-
chemical yield (RCY, determined by radioHPLC analysis of the crude
product) and Am (Table 1). The increase of the discharge time from 50
to 100 or 150 s did not result in any significant changes in RCY or Am.
However, when the discharge was carried out for 10 s only trace
amount of the desired product was observed.
For this study 6-[18F]fluoro-L-DOPA has been used as a model mo-
lecule to demonstrate the presence of 18F-labelled electrophilic species
and to facilitate radioHPLC analysis. It is
a well-known radio-
pharmaceutical, commonly used for the PET imaging of dopaminergic
systems [18]. The electrophilic 18F-fluorination reagent produced by
this method was also used for synthesis of [18F]Selectfluor bis(triflate)
[19] and subsequently [18F]F-DPA, a tracer for the imaging of the
translocator protein 18 kDa (TSPO) [20] (Fig. 1).
For the reactions carried out with a 4 times higher starting activity
the 6-[18F]fluoro-L-DOPA was isolated by semi preparative radioHPLC
and resulted in 22
purity (RCP) of 93
7 MBq of the final product with a radiochemical
7%.
For the reactions carried out in Ne only trace amounts of 6-[18F]
fluoro-L-DOPA were detected regardless of the duration of the dis-
charge (Fig. 2B).
2. Results and discussion
2.1. Formation of electrophilic 18F-fluorination reagents and synthesis of 6-
[
2.2. Spectrometric analysis
18F]fluoro-L-DOPA
Spectrometric analyses of the light emitted during the discharge
were carried out for both SF6/Xe and SF6/Ne gas mixtures.
Electrophilic 18F-fluorination reagents and subsequently 6-[18F]
91

A. Krzyczmonik et al.
JournalofFluorineChemistry204(2017)90–97
Fig. 2. A Chromatogram of the 6-[18F]fluoro-L-
DOPA synthesis carried out with SF6/Ne
B
Chromatogram of the 6-[18F]fluoro-L-DOPA synth-
esis carried out with SF6/Xe.
hydrogen (656 nm) and silicon (several emission lines in range of
243–253 nm) were detected.
Table 1
Results of the syntheses of 6-[18F]fluoro-L-DOPA with different duration of the discharge.
For Entry 7 a four times higher starting activity was used (for entries 1–6 starting activity
was 17
2 GBq). Radiochemical yields (RCY) and molar activities (Am) were de-
2.3. Labelling of [18F]Selectfluor bis(triflate) and [18F]F-DPA
termined based on radioHPLC of the crude product.Entry.
The electrophilic 18F-fluorination species made by discharge in SF6/
Xe were successfully used for the synthesis of [18F]Selectfluor bis(tri-
flate) (Fig. 5), which was confirmed by the radioLC–MS analysis of the
crude reaction mixture (Fig. 5A).
Matrix gas Discharge
time (s)
Activity of crude
product solution
(MBq)
Am (GBq/
μmol)
RCY (%)
N
1
2
3
4
5
6
7
Ne
Ne
Xe
Xe
Xe
Xe
Xe
10
100
10
47
–
–
–
0.4
1
3
1
3
3
3
5
The crude solution of [18F]Selectfluor bis(triflate) was used for the
synthesis of [18F]F-DPA resulting in 2% RCY and Am of 1.3 GBq/μmol
(Fig. 5B).
77
34
7
22
20
94
0.5
1
0.4
190
144
178
132
297
50
0.8
0.9
0.8
2.2
0.1
0.1
0.1
0.5
11
13
8
1
1
2
100
150
100
2.4. [18F]XeF2 analysis
23
9
RadioHPLC analysis of the solution of the gas mixture created
during discharge dissolved in MeCN did not indicate the presence of
Characteristic emission lines for fluorine and sulfur were observed in
the spectrum which was taken during discharge in the SF6/Ne gas
mixture (Fig. 3BNe and 3CNe). For the SF6/Xe mixture no emissions lines
for fluorine were observed (Fig. 3BXe). However, the characteristic
emission lines from sulfur were detected (Fig. 3CXe).
Ionic and atomic Xe emission lines were detected when the dis-
charge was carried out in SF6/Xe (Fig. 3DXe). The weak emission lines
at 260, 350, 460 nm are characteristic for both ionic Xe and the XeF*
excimer (Fig. 4) [21–23]. Ne emissions lines were also detected in the
SF6/Xe mixture since it was used as a transfer gas and therefore was
also present in the discharge chamber (Fig. 3DXe).
[
18F]XeF2. When the solution was co-injected with nonradioactive re-
ference of XeF2 and immediately analyzed by radioHPLC no [18F]XeF2
was detected (Fig. 6A). Analysis of the same solution after 20 min
showed traces of [18F]XeF2 produced by isotopic exchange. 4 h after
synthesis 12% of activity detected by radioHPLC corresponded to [18F]
XeF2 (Fig. 6B).
3. Discussion
Practically useful yields of electrophilic 18F-fluorination reagents
were obtained in the experiment where Xe was used as a matrix gas for
In both gas mixtures weak emission lines from oxygen (777 nm),
92

A. Krzyczmonik et al.
JournalofFluorineChemistry204(2017)90–97
Fig. 3. A Photographs and emission spectra of discharges carried out in SF6/Xe (left) or SF6/Ne (right). On graphs B, C and D x-axes present λ (nm) and y-axes Intensity (arb. units). B
Wavelength range in which strong emission lines from atomic fluorine are expected. Note that these emissions are present when Ne is used as a matrix but not in the Xe matrix. C
Wavelength range in which strong emission lines from atomic sulfur are expected. Note that atomic sulfur emission are observed from both matrixes. D Wavelength ranges where
characteristic emission from matrix gases are expected. Note that in Xe both atomic (neutral) and ionic emission are seen, as well as weaker Ne emission, which presence stems from
purification of [18F]MeF (see Section 5.3 [18F]MeF production). In Ne only atomic emission are seen from the matrix gas. No ionic emissions were observed.
93

A. Krzyczmonik et al.
JournalofFluorineChemistry204(2017)90–97
Fig. 4. Optical emission lines recorded from discharge carried out in SF6/Xe gas mixture, see also Fig. 3. The lines marked are putatively assigned to XeF*excimer [21–23].
the SF6/[18F]MeF discharge reaction. This was demonstrated by the
successful synthesis of 6-[18F]fluoro-L-DOPA and [18F]Selectfluor bis
(triflate). In contrast, when Ne was employed as the matrix gas low
yields were obtained. This suggest that Xe plays a crucial role in the
generation of electrophilic 18F-fluorination reagents.
Spectrometric data showed that no atomic fluorine is observed
during the discharge in Xe. At the same time there are clear signals from
atomic sulfur, atomic Xe and ionic Xe. This suggest that SF6 is atomized
during discharge but the fluorine immediately interacts with other
species. In addition, weak emissions lines at 260, 350 and 460 nm
(Fig. 4) were detected. While these have been reported to be emission
lines of atomic and ionic Xe they have also all been reported to be
characteristic emission lines for the Xe-F* excimer [21–23]. The pre-
sence of Xe-F* emission lines would explain the apparent absence of
atomic fluorine. Based on this finding we propose that excited Xe-F*
intermediate species are generated during the discharge.
When the discharge was carried out in Ne, a similar interaction did
not occur between Ne and F. Even though atomic fluorine was produced
and observed during the discharge, the Ne-F* species is not known to
exist. Suggesting that fluorine probably reorganizes into different S-F
species and hence only traces of the subsequent electrophilic 18F-
fluorination product can be detected.
RadioHPLC analysis of the solution of the gases generated during
discharge in Xe dissolved in MeCN confirmed that only negligible
amounts of [18F]XeF2 were produced in this process. This indicates that
the electrophilic reagent which was produced during the discharge is
indeed [18F]F2. Analysis of the solution containing the dissolved gas
and XeF2 reference showed that [18F]XeF2 is formed via 19F/18
F
Fig. 5. A radioLC–MS analysis of crude solution of
18F]Selectfluor bis(triflate) B radioHPLC chromato-
gram of crude solution of [18F]F-DPA.
[
94

A. Krzyczmonik et al.
JournalofFluorineChemistry204(2017)90–97
Fig. 6. RadioHPLC chromatograms of solutions
made by dissolving the crude gas products from the
high-voltage promoted reaction of [18F]CH3F/SF6/
Xe, the solutions also contained a nonradioactive
reference of XeF2. Chromatogram A was obtained
immediately after the synthesis, the analysis for
chromatogram B was performed 4 h after synthesis.
The [18F]XeF2 seen in chromatogram of panel B is
formed through 19F/18F isotopic exchange.
isotopic exchange reaction.
relatively high, 2.2 GBq/μmol, compared to molar activates of
0.1–1.3 GBq/μmol achieved by in-target production methods [2,4].
While the presented method is technically challenging, it is not more
demanding than previously reported methods [1–4,6] since it circum-
vents the use of non-radioactive F2 gas.
A previously reported method for the discharge-promoted produc-
tion of XeF2 was carried out using a 1:2 mixture of Xe and F2 [10,11].
The quartz reaction vessel was kept at room temperature and the mild
discharge was induced by induction coil for up to 10 h. In the presented
system, the energy provided by the discharge is high enough to break
S–F and C–F bonds in SF6 and MeF molecules, respectively. The strength
of these S–F and C–F bonds is higher than that of the Xe–F bond [11],
suggesting that XeF2 would not be stable under the discharge applied.
The results obtained for the syntheses of 6-[18F]fluoro-L-DOPA
using [18F]F2 produced from SF6/Xe mixture and varying lengths of the
high voltage discharge shows that SF6/Xe mixture needs a longer dis-
charge time (50–150 s) to promote the reaction than the reaction with
F2/Ne (10 s) [6]. The longer discharge needed for the production of
4. Conclusion
This proof-of-concept study shows that it is possible to produce a
relatively high molar activity electrophilic 18F-fluorination reagent
from SF6 and [18F]MeF. Particularly, we showed that when Xe was
employed as the matrix gas in the high voltage discharge reaction a
usable RCY was obtained.
The presence of Xe during the discharge is a critical factor for this
reaction since only low amounts of electrophilic 18F-labelling species
were generated when the reaction was performed in Ne.
Negligible amounts of [18F]XeF2 were observed as a product of the
discharge promoted reaction, thus we propose that the electrophilic
18F-fluorination reagent formed is [18F]F2 gas.
[
18F]F2 from SF6/Xe mixture is most probably caused by the formation
of different S–F species which are decomposed further to elemental
fluorine during discharge.
Production of 6-[18F]fluoro-L-DOPA, [18F]Selectfluor bis(triflate)
and subsequently [18F]F-DPA proved that the electrophilic labelling
reagent produced can not only be used for direct labelling, but also for
production of different electrophilic reagents such as [18F]Selectfluor
bis(triflate), which can be used for further synthesis.
The [18F]F2 generated by this method was successfully used for the
synthesis of 6-[18F]fluoro-L-DOPA and could also be converted into a
milder 18F-fluorination reagent such as [18F]Selectfluor bis(triflate)
which could subsequently be used for labelling reactions.
Further development of this method should be focused on in-
creasing the yield at this level of carrier which would also result in an
increase in molar activity.
This is a successful proof-of-concept study where we demonstrated
that it is possible to produce an electrophilic 18F-fluorination reagent
without the need for toxic fluorine gas. While there is need for opti-
mization with regard to RCY and Am, the molar activity is already
95

A. Krzyczmonik et al.
JournalofFluorineChemistry204(2017)90–97
5. Experimental
software (version 3.1.6) with a Waters Atlantis dC18, 3.9 × 150 mm
column (Waters Corp., Milford MA, USA), 7 mM aqueous KH2PO4 as the
eluent and a flow of 1 mL/min. UV-absorption was measured at a wa-
velength of 280 nm and the radioactivity was detected with a NaI(TI)
scintillation detector.
Am was determined from the analytical radioHPLC runs. The frac-
tion containing 6-[18F]fluoro-L-DOPA was collected and measured for
radioactivity. The UV detector was calibrated with known amounts of
nonradioactive 6-fluoro-L-DOPA. The molar amount of product was
calculated from the area of the corresponding UV peak.
For experiments performed with higher starting activity (Table 1,
entry 7) crude reaction mixture was diluted with 150 μL of NaOH and
1 mL of HPLC eluent (saline with 0.01% of AcOH and ascorbic acid
200 mg/L). Semi-preparative HPLC was performed using a Phenomenex
Luna 5 μ C18, 10 × 250 mm (Torrance, CA, United States) column with
flow = 4 mL/min.
5.1. General
All organic solvents were HPLC grade and purchased from Sigma-
Aldrich (Steinheim, Germany). Potassium carbonate (K2CO3), hydro-
bromic acid (HBr, 47%), iodomethane (MeI), potassium dihy-
drogenphosphate (KH2PO4), silver trifluoromethanesulfonate (AgOTf)
and lithium trifluoromethanesulfonate (LiOTf) were also purchased from
Sigma-Aldrich. Kryptofix 222 (K222) [4,7,13,16,21,24-hexaoxa-1,10-dia-
zabicyclo[8.8.8]hexacosane] and acetic acid (AcOH, 100%) were pur-
chased from Merck KGaA (Darmstadt, Germany). Sodium hydroxide
(NaOH, 10.8 M, 32%) was supplied by Riedel-de Haën (Seelze,
Germany). N-Formyl-3,4-di-tert-butoxycarbonyloxy-6-(trimethylstannyl)-
L-phenylalanine ethyl ester (FDOPA precursor) was purchased from ABX
(Radeberg, Germany). 18O enriched water for the production of 18F was
purchased from Rotem Industries Ltd. (Arava, Israel). Gases were sup-
plied by AGA, Linde group (Espoo, Finland). N,N-Diethyl-2-(2-(4-(tribu-
tylstannyl)phenyl)-5,7-dimethyl-pyrazolo[1,5-α]pyrimidin-3-yl)acet-
amide (F-DPA precursor) and 1-chloro-methyl-4-aza-1-azoniabicyclo
[2.2.2]octane triflate (Selectfluor precursor) were synthesised by pre-
viously described methods.
5.6. Syntheses of [18F]Selectfluor bis(triflate) and [18F]F-DPA
[
18F]F2 gas was produced by using SF6/Xe and the method de-
scribed above with 100 s discharge. [18F]Selectfluor bis(triflate) and
18F]F-DPA were synthesised according to previously described proce-
[
All RCYs were determined by radioHPLC of the crude product.
dures [19,20].
The crude solution of [18F]Selectfluor bis(triflate) was analyzed by
radioLC–MS (QTRAP, Applied Biosystems SCIEX, Toronto, Canada)
with Phenomenex Kinetex F5 2.1 × 100 mm, 2.6 μm (Torrance, CA,
United States) [24]. The crude solution of [18F]F-DPA was analyzed by
radioHPLC with Merck Chromolith Performance RP-18e (10 μm,
4.6 × 100 mm) column (Merck KGaA, Darmstadt, Germany) [20].
5.2. [18F]Fluoride production
[
18F]Fluoride was produced via 18O(p,n)18F nuclear reaction. 2.3 mL
of oxygen-18-enriched water was irradiated with a 18 MeV proton beam
from a CC-18/9 cyclotron (Efremov Scientific Institute of Electrophysical
Apparatus, St. Petersburg, Russia). The water solution containing [18F]
fluoride was passed through an anion exchange cartridge (QMA Sep Pak,
Waters Corporation, Milford, MA, USA) and the trapped [18F]fluoride
was eluted to the reaction vessel with a K2CO3/K222 solution.
5.7. Spectrometric analysis
Spectrometric analysis of light emission during discharge was car-
ried out with a Mechelle 7500 simultaneously recording optical spec-
trograph (Multichannel Instruments AB, Skarpnäck, Sweden) covering
the spectral range from 185 to 1160 nm. The nominal spectral resolving
power λ/ΔλFWHM = 5200 is approximately constant over the whole
wavelength range. The exposure time was 1 s. Light emitted during
discharge was collected and conducted into the spectrometer with an
Optran UV 1000/1060 BN optical fiber (CeramOptec GmbH, Bonn,
Germany).
5.3. [18F]MeF production
[
18F]Fluoride was added to a reaction vessel containing K222
(22–28 mg) and K2CO3 (6–8 mg) and followed by 1 mL of MeCN.
Azeotropic distillation was carried out at 100 °C for 4 min under a he-
lium flow. Two further additions of MeCN were made (2 × 1 mL) each
one flowed by 4 min evaporation. MeI in MeCN (1.5 mmol in 1 mL) was
added to the dry [18F]KF/K222 complex and the reaction mixture was
heated at 100 °C for 60–90 s. The resulting [18F]MeF was purified by
gas chromatography, using Ne as the transfer gas, and was trapped in a
stainless steel loop submerged in liquid N2 [6].
Spectra were taken during discharge of SF6 in both Ne or Xe.
5.8. [18F]XeF2 analysis
The gas mixture formed after the discharge of the SF6/Xe/[18F]MeF
mixture was bubbled through 700 μL of MeCN with nonradioactive
reference of XeF2.
5.4. [18F]F2 production
After trapping, the stainless steel loop containing [18F]MeF was
allowed to warm to room temperature and 1.2 μmol SF6 in Xe or Ne
(4 bar of 1% SF6 in Xe or Ne) were used to transfer the trapped [18F]
MeF in Ne to the quartz discharge chamber. The gas mixture was ex-
cited by a high voltage electrical discharge (32–36 kV, 400 μA) for 10,
50, 100 or 150 s. The resulting gas was subsequently used for the
synthesis of 6-[18F]fluoro-L-DOPA or [18F]Selectfluor bis(triflate).
The samples of the above mixture were analyzed by analytical
radioHPLC using a Sunfire C18, 5 μm, 250 mm × 4.6 mm column
(Waters Corp., Milford MA, USA) and HCOONH4 (25 mM) and MeCN
(55:45, v/v) as an eluent with 1 mL/min flow at λ = 250 nm [25–27].
5.9. Statistical analysis
The results were reported as means
SD. All the statistical ana-
5.5. Synthesis of 6-[18F]fluoro-L-DOPA
lyses were performed using Microsoft Excel 2010. The differences be-
tween the results obtained using different conditions were tested using
the unpaired t test. The differences were considered statistically sig-
nificant if p < 0.05.
The gas mixture produced during the high voltage discharge was
bubbled through a solution of FDOPA precursor (3–3.3 mg) in Freon-11
(600 μL) and AcOH (25 μL). The solvent was evaporated under Ne flow.
Deprotection was carried out in HBr (300 μL) at 130 °C for 5 min. The
reaction mixture was diluted with 150 μL of NaOH and 1 mL of HPLC
eluent (7 mM KH2PO4 solution).
Acknowledgments
This study was funded by the European Community’s Seventh
Framework Programme: FP7-PEOPLE-2012-ITN-RADIOMI-316882 and
by a grant from the Academy of Finland (no. 266891).
Analytical HPLC of the diluted reaction mixture was performed on a
VWR Hitachi LaChrom Elite system with EXChrom Elite Client/Server
96

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JournalofFluorineChemistry204(2017)90–97
[
18F]fluoride ion in micro-reactor and at production scale, J. Fluorine Chem. 131
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