Radiosynthesis and analysis of (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid

Brown, G., Soloviev, D. and Lewis, D. Y. (2023) Radiosynthesis and analysis of (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid. Molecular Imaging and Biology, 25(3), pp. 586-595. (doi: 10.1007/s11307-022-01793-3) (PMID:36525163) (PMCID:PMC10172245)

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Purpose: (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is an L-glutamate derivative used as a PET biomarker to assess intracellular redox status in vivo through targeting of the cystine/glutamate antiporter protein, xc− transporter. In this report, we describe a radiosynthesis of [18F]FSPG for use in PET studies that address specific challenges in relation to the radiotracer purity, molar activity, and quality control testing methods. Procedures: The radiosynthesis of [18F]FSPG was performed using a customised RNPlus Research automated radiosynthesis system (Synthra GmbH, Hamburg, Germany). [18F]FSPG was labelled in the 3-fluoropropylmoiety at the 4-position of the glutamic acid backbone with fluorine-18 via substitution of nucleophilic [18F]fluoride with a protected naphthylsulfonyloxy-propyl-L-glutamate derivative. Radiochemical purity of the final product was determined by radio HPLC using a new method of direct analysis using a Hypercarb C18 column. Results: The average radioactivity yield of [18F]FSPG was 4.2 GBq (range, 3.4–4.8 GBq) at the end of synthesis, starting from 16 GBq of [18F]fluoride at the end of bombardment (n = 10) in a synthesis time of 50 min. The average molar activity and radioactivity volumetric concentration at the end of synthesis were 66 GBq µmol−1 (range, 48–73 GBq µmol−1) and 343–400 MBq mL−1, respectively. Conclusion: Stability tests using a 4.6 GBq dose with a radioactivity volumetric concentration of 369 MBq mL−1 at the end of synthesis showed no observable radiolysis 3 h after production. The formulated product is of high radiochemical purity (> 95%) and higher molar activity compared to previous methods and is safe to inject into mice up to 3 h after production.

Item Type:Articles
Additional Information:The authors would like to acknowledge funding from Cancer Research UK for core funding to the CRUK Beatson Institute (A13827) and to David Lewis’ laboratory (A25006) and from the Beatson Cancer Charity and Beatson Endowment.
Glasgow Author(s) Enlighten ID:Lewis, Dr David
Authors: Brown, G., Soloviev, D., and Lewis, D. Y.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Molecular Imaging and Biology
ISSN (Online):1860-2002
Published Online:16 December 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Molecular Imaging and Biology 25(3): 586-595
Publisher Policy:Reproduced under a Creative Commons License

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