“In-loop” 18F-fluorination: A proof-of-concept study

Article abstract of DOI:10.1002/jlcr.3751

There is a great demand to develop more cost-efficient and robust manufacturing processes for fluorine-18 (¹⁸F) labelled compounds and radiopharmaceuticals. Herein, we present to our knowledge the first radiofluorination “in-loop,” where [

Full text of DOI:10.1002/jlcr.3751

Dahl Kenneth (Orcid ID: 0000-0003-2948-2042)
Short Note
“In-loop” 18F-fluorination: A proof-of-concept study
Kenneth Dahl1*, Armando Garcia1, Nickeisha A Stephenson1-3, and Neil
Vasdev1,3
1Azrieli Centre for Neuro-Radiochemistry, Research Imaging Centre, Centre for Addiction and
Mental Health, Toronto, Ontario, M5T-1R8, Canada.
2 University of the West Indies, Mona, Department of Chemistry, Kingston, Jamaica.
3 Department of Psychiatry, University of Toronto, Ontario, Canada.
*Corresponding author: kenneth.dahl@camhpet.ca
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Abstract
There is a great demand to develop more cost efficient and robust manufacturing processes for
fluorine-18 (18F) labelled compounds and radiopharmaceuticals. Herein, we present to our
knowledge the first radiofluorination “in-loop”, where [18F]triflyl fluoride was used as the
labelling agent. Initial development of the “in-loop” [18F]fluorination method was optimized
by reacting [18F]triflyl fluoride with 1,4-dinitrobenzene to form [18F]1-fluoro-4-nitrobenzene.
This methodology was then applied for the syntheses of two well-known radiopharmaceuticals,
namely, [18F]T807 for imaging of tau protein, and [18F]FEPPA for imaging the translocator
protein 18 KDa. Both radiotracers were synthesized and formulated using an automated
radiosynthesis module with non-decay corrected radiochemical yields of 27% and 29%
(relative [18F]F-), respectively. The overall syntheses times for [18F]T807 and [18F]FEPPA were
65 min and 55 min, respectively. In these cases our “in-loop” radiofluorination methodology
enabled us to obtain equal or superior yields compared with conventional reactions in a vial.
The radiochemical purities were >99% and the molar activities were >350 GBq/µmol at the
end-of-synthesis for both radiotracers. This novel method is simple, efficient, and allows for a
reliable production of radiofluorinated compounds and radiopharmaceuticals.
Keywords: Radiofluorination, Loop, Fluorine-18, PET, Radiochemistry
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Introduction
The success of molecular imaging with positron‐ emission tomography (PET) depends
on the availability of selective molecular probes labelled with positron‐ emitters, such as
fluorine‐ 18 (18F, t1/2 = 109.7 min) or carbon-11 (11C, t1/2 = 20.3 min). [1-3] The captive solvent
(“in-loop”) methodologies have been adopted for routine 11C-radiotracer syntheses because of
the simplicity, high radiochemical yields (RCY), speed, versatility and ease of automation.[4-10]
While the “in-loop” technology has shown advantages for 11C-radiopharmaceutical production,
18
isotopic labeling using the most common PET radionuclide, F has not yet been achieved.
With the increasing demand for new 18F-labelled PET radiotracers and their application in drug
development involving multi-centre clinical trials [2-3], there is a pressing need for new and
practical methods for the introduction of 18F into bioactive molecules.
Pees and co-workers recently disclosed the preparation of a novel gaseous [18F]fluoride
source, [18F]triflyl
fluoride ([18F]2,
Table 1).[11] The reaction of N,N-
bis(trifluoromethylsulfonyl)aniline (1) with aqueous [18F]fluoride ([18F]F-) yielded [18F]2 in
high radiochemical yields (RCY, >95%). [18F]2 is continuously distilled out from the reaction
vessel into a second vial containing dry aprotic solvent, in which dry [18F]fluoride is released in
presence of base. This method was used to effectively label a range of aromatic as well as
aliphatic compounds in moderated to high RCYs. In this proof-of-concept work, we present to
our knowledge, the first radiofluorination “in-loop”, where [18F]triflyl fluoride was used as the
labelling agent. Furthermore, this protocol was utilized to synthesize [18F]FEPPA[12] and
[18F]T807[13], two well-known radiopharmaceuticals that are routinely synthesized for human
PET neuroimaging of the translocator protein 18 KDa (TSPO) and tau protein, respectively.
[TABLE 1]
Results and Discussion
The “in-loop” 18F-fluorination method described herein consists of: (i) the initial
trapping of gaseous [18F]2 via base-mediated conversion to dry [18F]F-, followed by, (ii) “in-
18
loop” radiofluorination to form F-labelled products. Importantly, these steps are performed
directly in a stainless steel HPLC loop (Figure 1). For easy adoption of this method for routine
radiopharmaceutical production, we integrated the “in-loop” method to a commercial
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radiosynthesis module to carry out automated HPLC purification and formulation of the
labelled compounds.
[FIGURE 1]
Initial development of the “in-loop” [18F]fluorination method was optimized by
reacting [18F]2 with 1,4-dinitrobenzene to form [18F]1-fluoro-4-nitrobenzene ([18F]3, Table 1).
[18F]2 was prepared and delivered in a stream helium gas (5 mL/min) as previously described.[11]
This process in which aqueous and cyclotron produced [18F]F- is converted to [18F]2 and distilled
out from the initial formation vial (Figure 1) takes about 5 minutes. The conversion yield from
[18F]F- to [18F]2 was generally greater than 95%. However, in this study, the generated [18F]2 was
transferred to a pre-coated HPLC loop (2,4-dinitrobenzene (6 µmol), base (2 - 6 µmol) dissolved
in 200 µL anhydrous aprotic solvent) instead of being transferred to a vial. After heating (100
oC) the HPLC loop for 10 minutes the crude reaction mixture was transferred to an empty receiving
vial using the HPLC pump (5 mL/min for 2 min). The RCY shown in Table 1 is a combination
between the radiochemical purity (RCP, determined by radio-HPLC analysis) of the crude
reaction mixture and the measured [18F]2 trapping. Furthermore, during the initial condition
screening, solvents with high viscosity and boiling point, e.g. DMSO and DMF, were examined
as reaction media for two reasons: (i) solvents with high viscosity are commonly preferred for
captive solvent methods, and; (ii), to prevent issues related to pressure increases during loop
heating. To our delight, the desired 18F-labelled product was obtained in near quantitative yield
with tetraethylammonium bicarbonate (TEAB) as the base (Table 1, entries 1-2). Similar RCY
was obtained with Kryptofix 222 / potassium bicarbonate (KHCO3 / K222) was used as the base
(Table 1, entry 4). However, it should be mentioned that KHCO3 / K222 is sparingly soluble in
DMSO (the solution required mixing using a vortex over-night for complete dissolution).
Furthermore, as expected, only low amount of the desired product was formed at room temperature
(Table 1, entry 3). It is noteworthy, that the organic base, 2-tert-butylimino-2-diethylamino-1,3-
dimethylperhydro-1,3,2-diazaphosphorine (BEMP), also promotes the [18F]3 formation (Table 1,
entry 5), but a higher temperature was needed to reach completion (Table 1, entry 6). Finally, to
facilitate a direct comparison with the standard “in-vial” method, [18F]3 was synthesized (Table 1,
entry 7) using the optimal conditions established for the “in-loop” reaction (Table 1, entry 1).
As the “in-vial” method commonly requires reactions to be performed on a milliliter scale, all
reagent, including the solvent, were increased by a factor of five. Interestingly, although the
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measured RCP remained the same between the methods (97%), a significant decrease in the
trapping efficiency of [18F]2 was observed (15%), leading to an overall non-isolated RCY of
15±1% (n = 3, Table 1, entry 7). This significant difference in [18F]2 trapping between the two
methods could be explained by the high surface-to-volume ratio inside the loop.
This “in-loop” [18F]fluorination methodology was then applied for the syntheses of
[18F]T807 and [18F]FEPPA (Table 2). The synthesis of [18F]T807 has previously been reported
by several research groups in RCYs ranging from 14 – 32%.[13-17] [18F]T807 is commonly
18
produced via our two-step one-pot procedure[14], which entails firstly the nucleophilic F-
fluorination of the nitro- or tetramethylammonium based precursor compound, followed by
thermal boc-deprotection to form the desired product. Some laboratories employ an acidic
promoted deprotection however, this is not required for the reaction and is not easily
implemented on a standard HPLC loop, and therefore thermal deprotection was selected as the
preferred route. We made one minor alteration to the standard conditions (Table 1, entry 1), by
employing a higher temperature (130oC instead of 100oC) for the “in loop” reaction to promote
thermal deprotection. In this reactions, [18F]T807 was obtained in a non-isolated RCY of 42%
(Table 2, entry 1). Next, the concentration of base was evaluated (Table 2, entries 1 - 4). In
general, larger amounts of base improved the RCY. The highest RCY was obtained at a base
concentration of 10 µmol (49±5%, Table 2, entry 4).
We and others have previously reported the “in-vial” radiosynthesis of the [18F]FEPPA,
which generally proceeds in good radiochemical yield (RCY = 30–40 %).[12, 18] However, using
standard conditions for the “in-loop” 18F-fluorination failed to generate any product (Table 2,
entry 5). On the other hand, with KHCO3/K222 as base and CH3CN as the solvent, a non-isolated
RCY of 51±6% was reached (Table 2, entry 6). In a last attempt to further increase the yield,
BEMP was used as the fluorination base, however, a decreased RCY was obtained (Table 2,
entry 7).
[TABLE 2]
To further exemplify the utility of this newly developed methodology, starting with
⁓3.7 GBq (100 mCi) aqueous [18F]F-, [18F]T807 and [18F]FEPPA, were isolated using semi-
preparative HPLC followed by solid-phase extraction (SPE) to generate the final formulated
product. To achieve this, after completed reaction, the crude reaction mixture was injected
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directly onto the HPLC column for purification. [18F]T807 and [18F]FEPPA were obtained in
isolated (27 mCi and 29 mCi, respectively) and non-decay corrected RCYs (relative [18F]F-) of
27% and 29%, respectively. The overall syntheses time for [18F]T807 was 65 min and the
corresponding value for [18F]FEPPA was 55 min. The radiochemical purity (RCP) was >99%
and the molar activity (Am) >350 GBq/µmol at the end-of-synthesis.
Conclusion
A fully-automated “in-loop” [18F]fluorination procedure has been developed. Three
18
different F-labelled compounds were produced in high RCY and Am. This novel method is
simple, efficient, and allows for a reliable production of radiofluorinated compounds and
radiopharmaceuticals.
Acknowledgement
Thanks to all members of the PET Centers at Centre forAddiction and Mental Health (CAMH).
N.V. thanks the Azrieli Foundation and the Canada Research Chairs Program for support.
Methods
Materials and general methods
Unless otherwise stated, all reagents were obtained from commercially available
sources and used without further purification. No-carrier-added [18F]F- production was
performed using a MC17 cyclotron (Scanditronix).
The 18O(p,n)18F reaction was employed in a liquid target containing 10% [18O]H2O (dissolved
in 18 MΩ H2O) by bombardment with a 30 µA proton beam (16.4 MeV) for 30 min (producing
⁓3.7 GBq (100 mCi) [18F]F- at end-of-bombardment). The RCP and Am of the isolated products
were determined by reverse phase HPLC. Identification of all radioactive products was
confirmed by co-elution with the corresponding non-radioactive compound. The HPLC
analysis was performed using a high-pressure isocratic pump (Shimadzu LC-20AT) and a
variable wavelength UV-detector (λ = 254 nm, Shimadzu SPD-20A) in a series with a
radioactivity detector (Frisk-tech, Bicron) connected in series. The system was equipped with
a reverse phase analytical HPLC (4.6 х 250 mm, 5 µm, Phenomenex) and controlled by
PowerChrom chromatography software. Moreover, a modified Tracerlab FX2C module (GE)
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equipped with a C18 semi-preparative HPLC column as well as 5-mL HPLC loop was utilized
for automated purification and “in-loop” reaction platform.
General procedure for the “in-loop” fluorination of [18F]1-fluoro-4-nitrobenzene ([18F]3).
A schematic layout of the experimental design is shown in Figure 1. Prior to the start-
of-synthesis, the precursor compound, 2,4-dinitrobenzene (6 µmol), cryptand and/or base
(TEAB (2 µmol), K222 / KHCO3 (2 µmol), or BEMP (6 µmol)) dissolved in 200 µL solvent
(DMF or DMSO) was loaded to the HPLC loop (5-mL). In a typical experiment, cyclotron
produced [18F]F- was first concentrated on an ion-exchange column (Chromafix) from one side
and the accumulated [18F]F- was further eluted from the other side with 0.5 mL of aqueous 0.1
M K2SO4 solution into a 5-mL vial pre-charged with 4-6 mg of N,N-
bis(trifluoromethylsulfonyl)aniline (1, Table 1) in 1 mL of DMF. The resulting mixture was
heated (50oC, block heater, IKA) and the formed [18F]triflyl fluoride ([18F]2) was continuously
blown out with helium (5 µL/min) from the vial, first through a drying column (P2O5) and
finally into the pre-coated HPLC loop. This process in which aqueous and cyclotron produced
[18F]F- is converted to [18F]2 and distilled out from the initial formation vial and into the pre-coated
HPLC loop (Figure 1) takes about 5 minutes. [18F]2 was trapped by base-mediated conversion to
[18F]F- inside the HPLC loop. Unreacted [18F]2 was subsequently trapped quantitatively by an
ascarite trap (hydroxide-coated silica). The loop was then heated to the desired temperature for
10 min using a pre-heated oil bath. The crude reaction mixture was cooled to room temperature
and transferred to an empty receiving vial using the HPLC pump (5 mL/min for 2 min, CH3CN-
NH4CO2H (0.1 M) (30/70, v/v)). The non-isolated RCY was measured using radio-HPLC.
Synthesis of [18F]FEPPA.
Prior to the start-of-synthesis, FEPPA precursor (1.8 µmol), KHCO3 (2 µmol), K222 (2
µmol) dissolved in 200 µL CH3CN was loaded to the HPLC loop (5-mL) prior to the start-of-
synthesis. The formed [18F]2 was produced and transferred into the pre-coated HPLC loop. The
resulting mixture was heated to 80oC for 10 min. Following this reaction, the crude mixture
was cooled to room temperature and injected onto an HPLC column for purification and
subsequent formulation. [18F]FEPPA was purified using a reverse-phase HPLC on a Luna C-
18 column (250 mm x 7.8 mm, 10 µm, Phenomenex), and CH3OH-formic acid (0.5% in H2O)
(50/50, v/v) was used as the eluting solvent at a flow rate of 7 mL/min. The eluent was
monitored by a UV absorbance detector (λ = 254 nm) in series with a GM tube radioactivity
detector. The product was eluted at 20-22 min. The fraction of the desired compound was
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collected into a vial pre-filled with 25 mL sterile water and 2 mL of NaHCO3 solution (8.4%
in H2O) directly from the HPLC column. The collected fraction was then pushed by helium
pressure (1 Bar) through a SPE cartridge (SepPak tC18, Waters). The SPE was first washed
with 10 mL of sterile water and eluted using 1 mL of ethanol. The product was finally
formulated using 10 mL of saline (0.9% sodium chloride). The RCP and Am were determined
by reverse phase HPLC (4.6 х 250 mm, 5 µm, Phenomenex) and was eluted with acetonitrile-
NH4CO2H (0.1 M) (50/50, v/v) at a flow rate of 3 mL/min (retention time = 4 - 5 min).
Synthesis of [18F]T807.
Prior to the start-of-synthesis, T807 precursor (1.25 µmol), TEAB (10 µmol) dissolved
in 200 µL DMSO was loaded to the HPLC loop (5-mL) prior to the start-of-synthesis. The
formed [18F]2 was produced and transferred into the pre-coated HPLC loop. The resulting
mixture was heated to 130oC for 10 min. After this reaction, the crude mixture was cooled to
room temperature and injected onto an HPLC column for purification and subsequent
formulation. [18F]T807 was purified using reverse-phase HPLC on a Luna C-18 column (100
mm x 21.2 mm, 5 µm, Phenomenex), and CH3OH-NH4CO2H (0.1 M) (50/50, v/v) was used as
the eluting solvent at a flow rate of 9 mL/min. The eluent was monitored by a UV absorbance
detector (λ = 254 nm) in series with a GM tube radioactivity detector. The product was eluted
at 31-33 min. The fraction of the desired compound was collected into a vial pre-filled with 25
mL sterile water and 2 mL of NaHCO3 solution (8.4% in H2O) directly from the HPLC column.
The collected fraction was then pushed by helium pressure (1 Bar) through a SPE cartridge
(SepPak tC18, Waters). The SPE was first washed with 10 mL of sterile water and eluted using
1 mL of ethanol. The product was finally formulated using 10 mL of saline (0.9% sodium
chloride). The RCP and Am were determined by reverse phase HPLC (4.6 х 250 mm, 5 µm,
Phenomenex) and was eluted with CH3CN-NH4CO2H (0.1 M) (30/70, v/v) at a flow rate of 3
mL/min (retention time = 4 - 5 min).
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References
1.
2.
3.
Dahl K, Halldin C, Schou M. New methodologies for the preparation of carbon-11
labeled radiopharmaceuticals. Clin Transl Imaging. 2017;5(3): 257-289.
Miller PW, Long NJ, Vilar R, Gee AD. Synthesis of 11C, 18F, 15O, and 13N Radiolabels
for Positron Emission Tomography. Angew Chem Int Ed. 2008, 47(47):8998-9033.
Deng X, Rong J, Wang L, Vasdev N, Zhang L, Josephson L, Liang SH. Chemistry for
11
18
13
15
Positron Emission Tomography: Recent Advances in C‐ , F‐ , N‐ , and O‐
Labeling Reactions. Angew Chem Int Ed. 2019;58(9):2580-2605.
Devenport RJ, Pike VW, Dowsett K, Turton DR, Poole K. Automated chemoenzymatic
synthesis of no-carrier-added [carbonyl-11C]propionyl L-carnitine for pharmacokinetic
studies. Appl Radiat Isot. 1997;48(7):917-924.
4.
5.
6.
Wilson AA, Garcia A, Jin L, Houle S. Radiotracer synthesis from [(11)C]-iodomethane:
a remarkably simple captive solvent method. Nucl Med Biol. 2000;27(6):529-532.
Wilson AA, Garcia A, Houle S, Vasdev N. Utility of commercial radiosynthetic
modules in captive solvent [11C]‐ methylation reactions. J Label Compd Radiopharm.
2009; 52(11):490-492.
7.
Watkins GL, Jewett DM, Mulholland GK, Kilbourn MR, Toorongian SA. A captive
solvent method for rapid N-[11C]methylation of secondary amides: application to the
benzodiazepine, 4'-chlorodiazepam (RO5-4864). Int J Rad Appl Instrum A. 1988;39(5),
441-444.
8.
Jewett DM, Ehrenkaufer RL, Ram S. A captive solvent method for rapid radiosynthesis:
application to the synthesis of [1-11C]palmitic acid. Int J Appl Radiat Isot. 1985;36(8),
672-674.
9.
Dahl K, Collier TL, Chang R, Zhang X, Sadovski O, Liang SH, Vasdev N. “In-Loop”
[11C]CO2-Fixation: Prototype and Proof-of-Concept. J Label Compd Radiopharm.
2018;61(3):252-262.
10.
11.
12.
13.
Downey J, Bangarzone S, Hader S, Gee AD. J Label Compd. Radiopharm. In‐ loop
flow [11C]CO2 fixation and radiosynthesis of N,N′‐ [11C]dibenzylurea 2018;61(3):263-
271.
Pees A, Sewing C, Vosjan M, Tadino V, Herscheid J, Windhorst AD, Vugts DJ. Fast
and reliable generation of [18F]triflyl fluoride, a gaseous [18F]fluoride source. Chem Comm.
2018;54,10179-10182.
Wilson AA, Garcia A, Parkes J, MacCormick P, Stephenson KA, Houle S, Vasdev N.
Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral
benzodiazepine receptors. Nucl Med Biol. 2008;35(3):305-314.
Xia C-F, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q,
Liu C, Mocharla VP, Mu F, Su H. Szardenings K, Walsh JC, Wang E, Yu C, Zhang W,
Zhao T, Kolb HC. [18F]T807, a novel tau positron emission tomography imaging agent
for Alzheimer's disease. Alzheimers Dement. 2013;9(6):666-676.
Shoup TM, Yokell DL, Rice PA, Jackson RN, Livni E, Johnson KA, Brady TJ, Vasdev
N. A concise radiosynthesis of the tau radiopharmaceutical, [18F]T807. J Label Compd
Radiopharm. 2013;56(14):736-740.
14.
This article is protected by copyright. All rights reserved.

15.
16.
17.
Holt DP, Ravert HT, Dannals RF. Synthesis and quality control of [18F]T807 for tau
PET imaging. J Label Compd Radiopharm. 2016;59(10):411-415.
Gao M, Wang M, Zheng Q-H. Fully automated synthesis of [18F]T807, a PET tau tracer
for Alzheimer's disease. Bioorg Med Chem Lett. 2015;25(15):2953-2957.
Mossine AV, Brooks AF, Henderson BD, Hockley BG, Frey KA, Scott PJH. An
updated radiosynthesis of [18F]AV1451 for tau PET imaging. EJNMMI Radiopharm
Chem. 2017;2:7.
18.
erroterꢀn-Infante N, Balber T, Fꢁrlinger P, Bergmann M, Lanzenberger R, Hacker M,
Mitterhauser M, Wadsak W, [18F]FEPPA: Improved Automated Radiosynthesis,
Binding Affinity, and Preliminary in Vitro Evaluation in Colorectal Cancer. ACS Med
Chem Lett. 2018;9(3):177-181.
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Figure 1: Schematic drawing of the “in-loop” 18F-fluorination setup.
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Table 1. “In-loop” synthesis of [18F]1-fluoro-4-nitrobenzene ([18F]3) via [18F]2
[18F]2 trapped
RCP of
RCY of
Temperature
(oC)
Entry
(%)c
[18F]3 (%)d [18F]3 (%)e
Solvent
DMSO
DMF
DMSO
DMSO
DMSO
DMSO
Base
TEAB
100
100
r.t.
1
2
3
4
5
6
>99
>99
>99
>99
>99
>99
96
94
13
95
70
93
96±1(n=3)
94±1(n=2)
13±1(n=2)
95±1(n=2)
70
TEAB
TEAB
100
100
130
KHCO3 / K222
BEMP
BEMP
93±1(n=2)
7 b
TEAB
100
DMSO
15
97
15±1(n=2)
aConditions for “in-loop” reaction: 1,4-dinitrobenzene (6 µmol), Base (TEAB (2 µmol), KHCO3
/ K222 (2 µmol), BEMP (6 µmol)), solvent (200 µL), and 100 oC for 10 min. bConditions for “in-
vial” reaction: 1,4-dinitrobenzene (30 µmol), TEAB (10 µmol), solvent (1000 µL), and 100oC for
10 min. cPercentage of [18F]2 trapped in the loop (or vial, for “in-vial” reaction). dRadiochemical
e
purity (RCP) established with radio-HPLC analysis of the crude product. Non-isolated
radiochemical yield (RCY), RCY = ([18F]2 trapped * RCP) / 100.
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Table 2. “In-loop” formation of [18F]FEPPA and [18F]T807
[18F]T807
[18F]2 trapped
RCY of
Temperature
Entry
(%)b
[18F]3 (%)c
Solvent
DMSO
DMSO
DMSO
DMSO
(oC)
130
130
130
130
Base (µmol)
TEAB (2)
TEAB (4)
TEAB (6)
TEAB (10)
1
2
3
4
>99
>99
>99
>99
42
45
49
49±5 (n=3)
[18F]FEPPA
[18F]2 trapped
RCY of
Temperature
Entry
Base (µmol)
TEAB (2)
Solvent
DMSO
CH3CN
(oC)
100
80
(%)b
[18F]3 (%)c
5
6
>99
>99
<1
KHCO3/K222 (2)
51±6 (n=3)
CH3CN
80
7
BEMP (6)
>99
12
aConditions for “in-loop” reaction: precursor (FEPPA precursor (1.8 µmol), T807 precursor (1.25
µmol)), base (2 -10 µmol), solvent (200 µL), and 80 - 130 oC for 10 min. bPercentage of [18F]2
trapped in the loop. cNon-isolated radiochemical yield (RCY), based on the radiochemical purity
(RCP) established by radio-HPLC analysis of the crude product and combined with the percentage
[18F]2 trapped in the loop.
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