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Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

preprint
revised on 21.12.2020, 14:47 and posted on 22.12.2020, 09:38 by Richard Edwards, Hannah Greenwood, Timothy Witney

Purpose: (S)-4-(3-18F-Fluoropropyl)-ʟ-Glutamic Acid ([18F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system xC-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [18F]FSPG production are required. Here, we report a cassette-based method to produce [18F]FSPG at high radioactivity concentrations from low amounts of starting activity.

Procedures: An automated synthesis and purification of [18F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [18F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [18F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [18F]FSPG in phosphate-buffered saline. Subsequently, the [18F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.

Results: The optimized protocol produced [18F]FSPG in 38.4 ± 2.6% RCY and 96% radiochemical purity. Small alterations, including the implementation of a reverse elution and an altered hypercarb cartridge, lead to significant improvements in radiotracer concentration from <10 MBq/mL to >100 MBq/mL. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [18F]fluoride.

Conclusions: We have developed a robust and facile method for [18F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [18F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of cassettes for an ‘out the box’ synthesis on a synthesis module routinely used for clinical production make the method amenable to rapid and widespread clinical translation.

Funding

Detecting tumour resistance to treatment with positron emission tomography.

Wellcome Trust

Find out more...

C7893/A26233

C416/A23233

History

Email Address of Submitting Author

tim.witney@kcl.ac.uk

Institution

Kings College London

Country

United Kingdom

ORCID For Submitting Author

0000-0002-9475-2873

Declaration of Conflict of Interest

The authors declare that they have no conflicts of interest.

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Version 1 of preprint

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