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Improved Synthesis and Quality Control of [18F]PSMA-1007

Poster · July 2019

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Antje Fasel
ABX advanced biochemical compounds
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 ABX advanced biochemical compounds
Improved Synthesis and Quality Control of [ F]PSMA-1007
18

A. Fasel, R. Martin, D. Baumgart, S. Weidlich, M. Müller*

ABX advanced biochemical compounds, Radeberg, Germany

Objectives Experimental details

Since its first appearance in 20161, [18F]PSMA-1007
has become a promising radiotracer for Separation of n.c.a. [18F]-fluoride from [18O]-enriched water is accomplished via fixation of 18F-
prostate cancer imaging. Its fast blood clearance and its alternate route of excretion that bypasses fluoride on an anion exchange cartridge (Sep-Pak QMA Light cartridge). Subsequently, the activity is
the urinary tract makes it an ideal candidate for the diagnostic efficacy in patients with low PSA eluted using TBA·HCO3/EtOH/H2O solution and dried in vacuo. 18F-fluorination of the precursor (1.6
values and in patients with biochemical recurrence after radical prostatectomy.2 mg) is realised in 2 ml DMSO (for MX/Neptis modules). The mixture is heated at 105 °C for 10 min.
Since its first publication (Cardinale et al., 2017)3 describing the synthesis and quality control of Incorporation of [18F]fluoride is up to 95%. After labelling, the crude [18F]PSMA-1007 is purified using
[18F]PSMA-1007 we have further developed the synthesis in order to improve the product quality a reversed-phase cartridge system consisting of a cation exchange cartridge and a C18 cartridge in
and product stability. The aim of this poster is to inform about the changes in the one-step series. The final product is eluted with 5 ml 30 % ethanolic solution and diluted with 15 ml PBS buffer
radiosynthesis and its SPE purification and its quality control examinations. containing 400 mg of sodium ascorbate as stabilizer. Final product volume is 20 ml, synthesis time is
45 min.

Synthesis Quality control

The [18F]PSMA-1007 one-step synthesis with cartridge purification has been developed on 10 Modified HPLC conditions
different radiotracer modules (GE TRACERlab FX FN and MX, FASTlab platform, NEPTIS Column: Ascentis Express ES-C18 peptide (2.7 µm, 160A, 150 x 4.6 mm), Sulpelco
plug/perform and mosaic RS, IBA SYNTHERA+/V2, Trasis AllinOne, Scintomics GRP, Eckert & Mobile Phase: Phase A: Aqueous solution of 20 mM NaH2PO4, pH = 2.5
Ziegler modular lab, Sumitomo). A few changes have been introduced to the previously published Phase B: Acetonitrile
method: The counter ion of the precursor molecule was exchanged from trifluoroacetate to Gradient: Time Phase A [% V/V] Phase B [% V/V]
0 – 2 min 77 23
acetate. The labelling temperature has been raised to 105 °C for most radiotracer synthesizers.
2 – 14 min 77 à 70 23 à 30
Further, the final product is eluted with 5 ml 30% ethanol solution and formulated in 15 ml 14 – 17 min 70 à 40 30 à 60
phosphate buffered saline (PBS) containing 400 mg of sodium ascorbate. 17 – 21 min 40 60
21 – 21.5 min 40 à 77 60 à 23
21.5 – 26.5 min 77 23
Flow rate: 1.3 ml/min Column temperature: 30 °C
O O
Injection vol.: 20 µl Detection: 225 nm, Radioactivity
O O Buffer prep.: Dissolve 20 mmol NaH2PO4 in 1L of water, add 10 ml 1 M H3PO4 until
OH N OH N
NH
H
NH
H pH = 2.5 is reached, adjust pH if needed
O O
HN O HN O
[18F]F-, TBA
HN O HN O
Retention time: [18F]PSMA-1007: 10-12 min, Precursor: 5-6 min, OH-PSMA-1007: 6-7 min
O O
DMSO, 105°C
HN HN
OH HN CO2H OH HN CO2H

O OH O
CO2H
O OH O
CO2H Typical results of a recent [18F]PSMA-1007 synthesis are shown below: Synthesis on ORA Neptis
O NH O NH mosaic RS module, starting activity 50.7 GBq, 30.8 GBq of [18F]PSMA-1007 were obtained, 60.7 %
yield (ndc), activity concentration 1.5 GBq/ml. QC: pH: 7.5, [18F]Fluoride by radio TLC: 0.2 %, EtOH
N N
conc.: 6.1 %, TBA spot test: passed, HPLC results are shown at EOS:
CH3CO2 18
N F

Precursor [18F]PSMA-1007 Radio channel

Figure 1: Reaction scheme for the preparation of [18F]PSMA-1007.

Hardware and Reagent kit schemes

A B

Radio chromatogram of [18F]PSMA-1007 with 96.8% at 11.03 min, minor radioactive side products at
12.20 min (0.31 %), 12.75 min (2.11 %) and 13.57 min (0.80%).

C
D

UV chromatogram (225nm) of [18F]PSMA-1007 Peak for sodium ascorbate at 1.4 min, minor impurities at
6.25 min (1.4 µg/ml), 7.71 min (0.2 µg/ml), 8.30 min (0.9 µg/ml), 8.79 min (0.6 µg/ml), 8.97 (0.5 µg/ml),
“cold” PSMA-1007 at 11.02 min (1.3 µg/ml) and 13.98 min (0.7 µg/ml).

E F Radio TLC conditions: Water/ACN 4/6, Silica layer on aluminium support

spots for sodium ascorbate

TBA spot test (see picture on the right): use TLC plate with silica layer on
polymer or aluminium support, mobile phase: methanol/ammonia (25%) spot for
TBA residue
1000/5. Apply 2 µl of final solution together with 2 µl of TBA standard (0.2
mg/ml) on TLC plate, shortly dry it at ambient temperature, develop the plate in
mobile phase, dry it with cold air, put it into an iodine chamber (1 min), record
the result. For visualisation, please see: https://youtu.be/vcFj1UfWbnw
Figure 2: Hardware and reagent kit schemes for [18F]PSMA-1007 synthesis using following
synthesizers: A) GE TRACERlab MXFDG, B) IBA Synthera +/V2, C) GE Fastlab platform, D) Trasis sample positive
control
sample

AllinOne, E) GE TRACERlab FXFN and F) ORA Neptis (plug/perform/RS). Results:

The above described modifications of the synthesis resulted in better radiochemical yields (on most
synthesizers: 40-50 % (± 10 %, ndc)), improved radiochemical and chemical purities (see results
Kits and cassettes for the above-mentioned modules are available from ABX. For further above) and a better product stability (stable for > 10 h at 30 °C with activity concentrations up to 4.5
information please contact sales@abx.de or please visit our new homepage under
GBq/ml). All mentioned quality control methods have been validated according to ICH guidelines
www.abx.de.
Q2(R1). A monography draft has been submitted to the European Pharmacopoeia (N°: 3116).

References: 1) ] Giesel et al., Eur J Nucl Med Mol Imaging. 2016, 43(10):1929-30. 2) Giesel et al., J Nucl Med. 2018 Jul 24. pii: jnumed.118.212233. 3) Cardinale et al., Pharmaceuticals (Basel). 2017, 10(4), pii: E77.
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