Automation of [18F]fluoroacetaldehyde synthesis: application to a recombinant human interleukin-1 receptor antagonist (rhIL-1RA)

Article abstract of DOI:10.1002/jlcr.3393

[¹⁸F]Fluoroacetaldehyde is a biocompatible prosthetic group that has been implemented pre-clinically using a semi-automated remotely controlled system. Automation of radiosyntheses permits use of higher levels of [¹⁸F]fluoride whilst

Full text of DOI:10.1002/jlcr.3393

Research article
Received 19 August 2015,
Revised 04 January 2016,
Accepted 29 February 2016
Published online 6 April 2016 in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/jlcr.3393
18
Automation of [ F]fluoroacetaldehyde
synthesis: application to a recombinant human
interleukin-1 receptor antagonist (rhIL-1RA)†
a
a
a
b
*
Olivia Morris, Adam McMahon, Herve Boutin, Julian Grigg, and
Christian Prenanta
[
18F]Fluoroacetaldehyde is a biocompatible prosthetic group that has been implemented pre-clinically using a
semi-automated remotely controlled system. Automation of radiosyntheses permits use of higher levels of [18F]fluoride
whilst minimising radiochemist exposure and enhancing reproducibility. In order to achieve full-automation of
[
18F]fluoroacetaldehyde peptide radiolabelling, a customised GE Tracerlab FX-FN with fully programmed automated
synthesis was developed.
The automated synthesis of [18F]fluoroacetaldehyde is carried out using a commercially available precursor, with
reproducible yields of 26% 3 (decay-corrected, n = 10) within 45 min. Fully automated radiolabelling of a protein,
recombinant human interleukin-1 receptor antagonist (rhIL-1RA), with [18F]fluoroacetaldehyde was achieved within 2 h.
Radiolabelling efficiency of rhIL-1RA with [18F]fluoroacetaldehyde was confirmed using HPLC and reached 20% 10 (n = 5).
Overall RCY of [18F]rhIL-1RA was 5% 2 (decay-corrected, n = 5) within 2 h starting from 35 to 40 GBq of [18F]fluoride.
Specific activity measurements of 8.11–13.5 GBq/μmol were attained (n = 5), a near three-fold improvement of those
achieved using the semi-automated approach.
The strategy can be applied to radiolabelling a range of peptides and proteins with [18F]fluoroacetaldehyde analogous to
other aldehyde-bearing prosthetic groups, yet automation of the method provides reproducibility thereby aiding
translation to Good Manufacturing Practice manufacture and the transformation from pre-clinical to clinical production.
Keywords: [18F]fluoroacetaldehyde; [18F]rhIL1RA; protein radiolabelling; prosthetic group; PET
being covalently linked to the peptide under mild reaction
Introduction
conditions are used. [18F]Fluoroacetaldehyde is an important
Positron emission tomography (PET) is an imaging modality
prosthetic group owing to its small size and, importantly, its
permitting quantitative non-invasive in-vivo molecular imaging;
its increasing popularity in a clinical setting is attributable to its
sensitivity and ability to identify unique biomarkers of disease
and capacity to classify physiological processes at the molecular
solubility in water thereby removing the requirement for organic
solvents that might denature a protein or peptide. The volatility
of fluoroacetaldehyde permits purification via distillation,
eliminating the requirement for solid phase extraction (SPE) or
high performance liquid chromatography (HPLC) separation.3 To
level. The ability to automate radiotracer synthesis has been key
in the advancement of PET.1 It not only improves reproducibility
which eases transition to Good Manufacturing Practice (GMP)
manufacture, a key objective of novel radiotracer development,
but also allows GBq scale quantities of [18F]fluoride to be used
with minimal radiochemist exposure. The GE TRACERLab FX
series of synthesisers are commonly used as radiochemistry
platforms, and a customised FX-FN system has been used
to automate the [18F]fluoroacetaldehyde synthesis originally
described by Prenant et al.2,3 which used a semi-automated
experimental setup.
date, [18F]fluoroacetaldehyde has been successfully implemented
in a pre-clinical trial using [18F]fluoroacetaldehyde radiolabelled
recombinant human interleukin-1 receptor antagonist (rhIL-1RA),
aWolfson Molecular Imaging Centre, CRUK and EPSRC Cancer Imaging Centre in
Cambridge and Manchester, The University of Manchester, Manchester, UK
bGE Healthcare, Life Sciences, Imaging R&D, The Grove Centre, Amersham, Bucks,
UK
*Correspondence to: Olivia Morris, Wolfson Molecular Imaging Centre, CRUK and
EPSRC Cancer Imaging Centre in Cambridge and Manchester, The University of
Manchester, Manchester, UK.
E-mail: olivia.morris-2@postgrad.manchester.ac.uk
†Additional supporting information may be found in the online version of this
[18F]Fluoride is
a PET radioisotope with a number of
advantageous features including 97% positron emission, a low
positron energy and a 109.8-min radioactive half-life, which
permits more extensive radiochemical syntheses yet also limits
patient dose.4,5
article at the publisher’s web-site.
Peptides and proteins are complex and have multiple
functionalities that are incompatible with direct fluorination using
This is an open access article under the terms of the Creative Commons
Attribution License, which permits use, distribution and reproduction in
[18F]fluoride. It is for this reason that prosthetic groups capable of any medium, provided the original work is properly cited.
J. Label Compd. Radiopharm 2016, 59 277–283
Copyright © 2016 The Authors. Journal of Labelled Compounds
and Radiopharmaceuticals published by John Wiley & Sons, Ltd.

O. Morris et al.
17.5kDa.2 Radiosynthesis of [18F]fluoroacetaldehyde from [18F] (0.7 ml). The mixture was azeotropically dried at 110 °C with 3
fluoride achieved radiochemical yields (RCY) of 31–37% in a two- sequential additions of acetonitrile (3 × 0.5 ml).
step, one-pot reaction scheme.3 This was achieved in a semi-
automated synthesis using a remotely controlled experimental
system and reached overall RCY of [18F]rhIL-1RA ranging from 7.1
to 24.2%.2
[
18F]Fluoroethyltoslyate (FEtTos)
A solution of ethylene di-p-toluenesulphonate (5 mg, 13.5 μmol)
in DMSO (150 μl) was added from Vial 3 (V3 on Figure 2) to dried
[18F]KF/Kryptofix complex in Reactor 1. The reactor was then
heated to 80 °C and cooled to 50 °C after 10 min HPLC analysis
of the crude reaction mixture was performed to measure [18F]
FEtTos RCY using a Prodigy column (10 μm, ODS (3), 100 Å.
250 × 10 mm Phenomenex UK, Macclesfield, Cheshire UK) eluted
with acetonitrile:water 50:50, 6 ml/min, 254 nm, tR = 9 min.
Here, we describe the fully-automated synthesis of [18F]
fluoroacetaldehyde and subsequent radiolabelling of rhIL-1RA
using a modified GE TRACERLab FX-FN. Radiolabelling of rhIL-
1RA with [18F]fluoroacetaldehyde permits direct comparison
between the methods of Prenant et al.2 and the present study.
Figure 1a shows the reaction mechanism for the synthesis
of [18F]fluoroacetaldehyde, whilst Figure 1b illustrates the
mechanism of rhIL-1RA reductive alkylation with [18F]
fluoroacetaldehyde.
[
18F]Fluoroacetaldehyde
Experimental
To the reactor containing [18F]FEtTos in DMSO was added DMSO
(150 μl) from vial 4 (V4 on Figure 2). The reactor was then heated
to 160 °C for 5 min, and a route from Reactor 1 to Reactor 2 was
opened (through V5). [18F]Fluoroacetaldehyde was distilled and
collected in Reactor 2 containing pH 6 citrate buffer (150 μl,
20 mM). Distillation proceeded for 4 min to minimise DMSO
carry-over. RCY 26% 3 (decay-corrected, n = 10).
All solvents were purchased from Sigma-Aldrich (Gillingham, Dorset, UK)
and used without further purification. rhIL-1RA (100 mg/ml), anakinra
(Kineret) was provided by Amgen (Thousand Oaks, CA, USA) in a
formulated solution containing 100-mg anakinra, 1.29-mg sodium citrate,
5.48-mg sodium chloride, 0.12-mg disodium EDTA and 0.70-mg
polysorbate 80 in 1-ml water.
[
18F]Fluoride was produced onsite via the 18O(p, n)18F nuclear reaction
by 16.4-MeV proton bombardment of enriched [18O]H2O using a GE
(Amersham, Bucks, UK) PETtrace cyclotron.
18F]rhIL-1RA
Analytical HPLC was performed using a Shimadzu (Milton Keynes, UK)
Prominence system (LC-20AB solvent delivery system, SPD-20A dual
wavelength absorbance detector) controlled by LabLogic (Sheffield, UK)
Laura 3 software via a CBM-20A controller. HPLC eluate was measured
for radioactivity using a Bioscan (Oxford, UK) Flowcount B-FC 3100
gamma detector. All pre-clinical PET scans were carried out using a
Siemens (Oxford, UK) Inveon® PET-CT scanner.
[
[18F]Fluoroacetaldehyde was transferred from Reactor 2 to Reactor 3
(see Figure 2) containing a solution of rhIL-1RA (30 μl, 1.7 μmol),
sodium cyanoborohydride in a solution of pH 6 citrate buffer
(10 μl, 1.0 M) and pH 6 citrate buffer (55 μl, 20 mM) before
heating to 40 °C for 20 min. [18F]Fluoroacetaldehyde radiolabelled
rhIL-1RA was purified using SE-HPLC (GE Superdex 200 10/300 GL,
PBS, 1 ml/min, 254 and 220 nm, tR = 15 min) and analysed for quality
control purposes using analytical SE-HPLC (GE Superdex 200 10/300
GL, PBS eluent, 0.6 ml/min, 254 and 220 nm, tR = 15min). Overall RCY
Radiosynthesis, GE TRACERLab FX-FN
[
18F]Potassium fluoride
Cyclotron produced [18F]Fluoride was trapped on a Sep-Pak and specific activity measurements of 5% 2 and 8.11–13.5 GBq/μ
QMA cartridge (Oasis, Waters, Wilmslow, UK) then eluted with mol respectively (decay-corrected, n= 5). Specific activity
K2CO3 solution (4 μmol, 0.4 ml) into a 3-ml vial (Reactor 1 on measurements were calculated using a standard of rhIL-1RA as a
Figure 2) containing Kryptofix 222 (3 mg, 8 μmol) in acetonitrile reference for HPLC analysis.
Figure 1. (a) Reaction mechanism for the radiosynthesis of [18F]fluoroacetaldehyde. (b) Reaction mechanism for the radiolabelling of rhIL-1RA through reductive
alkylation.
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Copyright © 2016 The Authors. Journal of Labelled Compounds
and Radiopharmaceuticals published by John Wiley & Sons, Ltd.
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O. Morris et al.
Figure 2. Schematic of GE TRACERlab FX-FN setup.
[
18F]fluoroacetaldehyde-2,4-DNPH
Pre-clinical PET imaging
Derivatisation of [18F]fluoroacetaldehyde was performed using All animal handling was in accordance with UK legislation under
the methodology reported by Prenant et al.3 In short, 2,4- the 1986 Animals (Scientific Procedures) Act. The pre-clinical
dinitrophenylhydrazine (DNPH) (25 μl, 5 μmol) was added to methodology followed was as described by Cawthorne et al. in
[18F]fluoroacetaldehyde (30 μl) in ethanol (60 μl). The solution 2011.6 In short, one C57Bl6 mouse and one Sprague–Dawley
was heated for 15 min at 90 °C before HPLC analysis rat were anaesthetised using isoflurane (induction 4% and
(Phenomenex Prodigy C18, 10 μm, ODS (3), 100 Å. 250 × 10 mm, maintained 1.5%) in 70% N2O and 30% O2 mixture. [18F]rhIL-
acetonitrile:water 50:50, 3 ml/min, 360 nm, tR = 25 min).
1RA was injected in the tail vein (17.9 MBq for the mouse and
21.4 MBq for the rat). The scans were performed on a Siemens
Inveon® PET-CT scanner. The acquisition protocol consisted of
the following parameters: a CT scan was performed prior to the
PET acquisition to obtain the attenuation correction factors.
PET data were acquired over 1 h with the time coincidence
window set to 3.432 ns and the levels of energy discrimination
set to 350 keV and 650 keV. The list mode acquisition data files
were histogrammed into 3D sinograms with a maximum ring
difference of 79 and span 3. The list mode data of the emission
scans were sorted into 16 dynamic frames (5 × 1 min, 5 × 2 min,
3 × 5 min, 3 × 10 min). Finally, the emission sinograms (each
frame) were normalised, corrected for attenuation, scattering
and radioactivity decay, and reconstructed using OSEM3D (16
subsets and 4 iterations) into images of dimensions 1282
(transaxially) × 159 (longitudinally) with 0.776× 0.776 × 0.796 mm-
voxels (FOV diameter: 99.3 mm× 126.6mm longitudinally).
Synthesis of reference compounds
Synthesis of fluoroacetaldehyde
Fluoroacetaldehyde was prepared as per the methodology
reported by Prenant et al.3 In short, fluoroethanol (62 μl, 1 mmol)
was added to pyridinium dichromate (PDC) (576 mg, 1.5 mmol)
in dichloromethane (DCM) (1.5 ml) and was stirred at room
temperature for 24 h. The liquid portion was removed from the
PDC precipitate and then heated to 80 °C. The distillate of which
was collected in deionised H2O (1 ml), and a sample of aqueous
phase, containing the fluoroacetaldehyde, was used for HPLC
analysis (Phenomenex Prodigy C18, 10 μm, ODS (3), 100 Å.
250 × 10 mm, water eluent, 2 ml/min, 277 nm, tR = 8 min).
Synthesis of fluoroacetaldehyde-2,4-DNPH
Results and discussion
To the fluoroacetaldehyde solution (0.5 ml) 2,4-DNPH phosphoric A schematic of the customised GE TRACERlab FX-FN can be seen
acid solution (0.8 ml, 0.2 M) was added, and the mixture was in Figure 2. The modifications permitting automated [18F]
heated to 90 °C for 15 min before HPLC analysis (Phenomenex fluoroacetaldehyde synthesis and subsequent rhIL-1RA
Prodigy C18, 10 μm, ODS (3), 100 Å. 250 × 10 mm, acetonitrile: radiolabelling will now be discussed alongside details regarding
water 50:50, 3 ml/min, 360 nm, tR = 25 min).
process development and finally [18F]rhIL-1RA pre-clinical results.
J. Label Compd. Radiopharm 2016, 59 277–283
Copyright © 2016 The Authors. Journal of Labelled Compounds
and Radiopharmaceuticals published by John Wiley & Sons, Ltd.
www.jlcr.org

O. Morris et al.
Addition of a third reactor
A distillation time of 4 min was sufficient to reach a plateau in
the RCY of [18F]fluoroacetaldehyde. Additional time resulted in
further DMSO carry-over.
A third reactor was added to the GE TracerLab FX-FN in order
to mitigate issues of detrimental peptide foaming upon
prolonged exposure to a gas flow. The process of [18F]
fluoroacetaldehyde distillation requires constant helium flow
at 15 ml/min and, in order to collect the volatile product, it
is necessary to distill the [18F]fluoroacetaldehyde into a
solution; it was found that this process caused excessive
Prenant et al.2 describe a flow-rate of 7–8 ml/min in the
reductive alkylation of rhIL-1RA with [18F]fluoroacetaldehyde.
Therefore a flow-meter and needle-valve, connected to valve 6,
were incorporated in the automated setup to control the helium
flow for the distillation step between Reactor 1 and Reactor 2. A
flow-rate of 15 ml/min was found to produce the optimal
distillation conditions.
foaming of the peptide and prevented
a high-yielding
reaction. In the current setup, [18F]fluoroacetaldehyde is
distilled into citrate buffer pH 6 (150 μl), in a second reactor,
and this solution is then transferred to a third reactor. The
ability to both retract and insert the needle in to and out of
the solution in Reactor 3 was an important modification. In
the first instance, addition of the [18F]fluoroacetaldehyde/
buffer solution whilst the needle is in a retracted position
ensures minimal exposure of the peptide to helium flow. Once
[18F]Fluoroacetaldehyde syntheses reproducibly attained RCY
of 26% 3 (decay-corrected, n = 10) within 45 min starting from
35 to 40 GBq of [18F]fluoride.
Synthesis of [18F]FEtTos in DMSO to remove acetonitrile
evaporation step
Block et al.7 report synthesising [18F]FEtTos in acetonitrile,
achieving appreciable RCY >90% within 10 min. The
the transfer of
[ 2 is
18F]fluoroacetaldehyde to Reactor
synthesis of
[
18F]fluoroacetaldehyde requires Kornblum
complete, the needle can be lowered into the reaction
mixture to be transferred to the HPLC loop and injected onto
the HPLC column. This, therefore, required the reactor head to
be moved from its original position at Reactor 1 to Reactor 3.
A buffer volume of 150 μl in Reactor 2 was required to
minimise the degree of loss during the transition from Reactor
2 to 3. As a result, the peptide reaction mixture volume in
Reactor 3 was kept to a minimum to maintain a high
concentration for radiolabelling.
oxidation thus requiring DMSO. As a result of this and for
ease of automation, the synthesis of [18F]FEtTos in DMSO
was investigated. Figure 3 gives the radio-UV-chromatogram
data from the synthesis of [18F]FEtTos in DMSO, achieving
reproducible RCY of 60%. As a consequence of this, DMSO
was used for the synthesis of [18]FEtTos. [18F]FEtTos can be
seen at 9 min, and the ditosylate precursor can be seen in
the UV chromatogram at 25 min.
It should be noted that, despite DMSO being used to carry
out [18F]FEtTos synthesis, an additional DMSO aliquot was
required for the Kornblum oxidation and production of
Distillation reaction conditions
[
18F] fluoroacetaldehyde. This may be attributable to
Distillation was carried out using Reactors 1 and 2. As the reactor
head had to be moved from Reactor 1 to Reactor 3, it was
necessary to produce a home-made reactor, with silicon septum
screw top, that fitted directly into the heating block, as can be
seen in Figure 2.
degradation of the initial DMSO aliquot used during [18F]
FEtTos synthesis.
[
18F]Fluoroacetaldehyde characterisation with 2,4-DNPH
A temperature of 160 °C was required for distillation of [18F]
fluoroacetaldehyde from Reactor 1 to 2. This temperature The synthesis of [18F]fluoroacetaldehyde was confirmed by
achieved a reproducible RCY of the prosthetic group and derivatisation to the corresponding hydrazone followed by
minimised the degree of DMSO carry-over into the second radio-HPLC analysis. 2,4-DNPH was used as the derivatising
reactor. It was established that an increase in reactor 1 agent.8
temperature from 160 °C to 170 °C had minimal impact on
Figure 4 gives the radio-UV-chromogratogram data from a co-
the RCY of
[
18F]fluoroacetaldehyde and increased the injection of isotopically unmodified-fluoroacetladehyde-2,4-DNPH
amount of DMSO carry-over into Reactor 2, an undesirable solution and [18F]fluoroacetaldehyde-2,4-DNPH solution. 2,4-DNPH
result owing to the sensitivity of some peptides and has a retention time of approx. 10 min and co-elution of the
proteins to DMSO.
corresponding hydrazone complex for both [18F]fluoroacetaldehyde
Figure 3. Radio- and UV-chromatogram for the radiosynthesis of [18F]FEtTos in DMSO.
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and Radiopharmaceuticals published by John Wiley & Sons, Ltd.
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O. Morris et al.
Figure 4. Radio- and UV-chromatogram for the characterisation of [18F]fluoroacetaldehyde with 2,4-DNPH.
and isotopically unmodified fluoroacetaldehyde is seen at
The relatively low RCY can be expected from reductive
approximately 24 min.
alkylation, on account of the concentration dependence of the
second order rate kinetics and thus the relatively slow rates of
reaction.9 The radiolabelling of
a
protein with [18F]
Radiolabelling of rhIL-1RA with [18F]fluoroacetaldehyde
fluoroacetaldehyde is not, however, limited to reductive
alkylation, and the strategy can be used to site-specifically
Radiolabelling of rhIL-1RA with [18F]fluoroacetaldehyde was radiolabel aminooxy- or hydrazide-functionalised peptides or
carried out at 40 °C for 20 min. Radiolabelling efficiency of rhIL- proteins. Additionally, the requirement to use larger reaction
1RA with [18F]fluoroacetaldehyde was confirmed using HPLC volumes in order to efficiently transfer reaction mixtures around
and reached 20% 10 (n = 5). The radio- and UV-chromatogram the platform can negatively impact the RCY. Higher RCY were
can be seen in Figure 5.
attained under reductive alkylation in the original publication
The SE-HPLC chromatogram shows the [18F]rhIL-1RA at 9 min by Prenant et al.; however, the process was not compatible for
and [18F]fluoroacetaldehyde at 19 min. A side-product is also translation to an automated platform.2,3 In the semi-automated
observed at 23 min, thought to be as a result of a competing procedure, a sephadex gel was used to stabilise the rhIL-1RA
reaction with the reducing agent. This would be resolved under which is prone to foaming, as described.2 It was not possible to
chemical-ligation conditions on account of the enhanced stabilise the protein in this manner using the automated
stability of an oxime or hydrazide which negates the platform on account of the following SE-HPLC purification
requirement of a reducing agent.
step. Despite the automated synthesis attaining lower overall
The overall RCY of [18 F]rhIL-1RA was 5% 2 (decay-corrected, RCY than the semi-automated configuration, the enhanced
n = 5) starting from 35 to 40 GBq of [18F]fluoride. Specific activity reproducibility and considerable specific activity improvements
measurements of 8.11–13.5 GBq/μmol were attained (n = 5) are significant advantages to use of the automated method.2
using the automated method as opposed to 813.15–
Importantly, [18F]fluoroacetaldehyde radiolabelling occurs in
5040.2 MBq/μmol achieved using the semi-automated aqueous conditions and at low temperatures without the
approach.2 This significant increase in specific activity is a requirement for a high concentration of organic solvent, unlike
considerable advantage to the employ of the automated other [18F]prosthetic groups such as [18F]fluorobenzaldehyde.
method and is a result of the ability to use higher starting levels Such conditions are likely to be more suitable for peptides and
of radioactivity (35–40 GBq compared to 1.73–3.42 GBq).
proteins. Figure 6 shows the quality control (QC) analysis of the
Figure 5. Crude reaction mixture of [18F]fluoroacetaldehyde and rhIL-1RA.
J. Label Compd. Radiopharm 2016, 59 277–283
Copyright © 2016 The Authors. Journal of Labelled Compounds
and Radiopharmaceuticals published by John Wiley & Sons, Ltd.
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O. Morris et al.
Figure 6. Quality control of [18F]fluoroacetaldehyde labelled rhIL-1RA.
formulated [18F]fluoroacetaldehyde labelled rhIL-1RA. The SE- black) and the previous published work (shown in grey) which
HPLC chromatogram shows good radiochemical purity of the used a semi-automated [18F]rhIL-1RA radiosynthetic approach.6
final radiolabelled product, although a small shoulder can be The level quantified in the heart is lower than previously reported6
seen on the peak attributable to a dimer of the rhIL-1RA. This which is thought to be attributable to the absence of attenuation
was also reported by Prenant et al. in 2010.2
and scatter correction with the HIDAC scanner previously used
when compared to the Inveon scanner used in the present study.
Pre-clinical results
Summary
8F]rhIL-1RA was pre-clinically assessed using both wild type rat
and mouse models and can be seen in Figure 7. According to We report upon an automated radiosynthesis of [18F]
pre-clinical analyses, the biodistribution shows no defluorination fluoroacetaldehyde and its successful application in
as would be evidenced by [18F]fluoride bone uptake. Preferential radiolabelling rhIL-1RA. [18F]Fluoroacetaldehyde syntheses
distribution of [18F]rhIL-1RA in the kidneys and renal excretion reproducibly attained RCY of 26% 3 within 45 min (decay-
was seen, as previously described by Cawthorne et al.,6 signifying corrected, n = 10) starting from 35 to 40 GBq of [18F]fluoride.
preservation of rhIL-1RA integrity.
The automated platform additionally permitted successive
The time activity curves (TAC) (see Supporting Information, radiolabelling of a protein with [18F]fluoroacetaldehyde. The
Figure 1) show the concentration of [18F]rhIL-1RA over time in 17.5-kDa protein, rhIL-1RA, was radiolabelled with [18F]
the kidneys (cortex) and heart ventricle. The TAC presented show fluoroacetaldehyde with labelling efficiencies of 20% 10
agreement between data acquired in the current work (shown in (n = 5), achieving overall RCY of 5% 2 within 2 h (decay-
Figure 7. Mean intensity projection images of a mouse (A) and a rat (B) after injection of [18F]rhIL-1RA.
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Copyright © 2016 The Authors. Journal of Labelled Compounds
and Radiopharmaceuticals published by John Wiley & Sons, Ltd.
J. Label Compd. Radiopharm 2016, 59 277–283

O. Morris et al.
corrected, n = 5) starting from 35 to 40 GBq of [18F]fluoride.
Specific activity measurements of 8.11–13.5 GBq/μmol were
achieved (n = 5). Use of the automated radiosynthesis of
[18F]fluoroacetaldehyde and subsequent rhIL-1RA labelling not
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Acknowledgements
We gratefully acknowledge the support of the MRC and GE
Healthcare for funding the project. This work was supported by
CRUK/EPSRC [C8742/A18097].
The authors would like to thank members of the
radiochemistry and pre-clinical teams at Wolfson Molecular
Imaging Centre.
Supporting information
Additional supporting information may be found in the online
version of this article at the publisher’s web-site.
J. Label Compd. Radiopharm 2016, 59 277–283
Copyright © 2016 The Authors. Journal of Labelled Compounds
and Radiopharmaceuticals published by John Wiley & Sons, Ltd.
www.jlcr.org