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

Purpose: (S)-4-(3- ¹⁸ F-Fluoropropyl)-ʟ-Glutamic Acid ([ ¹⁸ F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x _C ^- , whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [ ¹⁸ F]FSPG production are required. Here, we report a cassette-based method to produce [ ¹⁸ F]FSPG at high radioactivity concentrations from low amounts of starting activity.
Procedures: An automated synthesis and purification of [ ¹⁸ F]FSPG was developed using the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [ ¹⁸ F]FSPG and by assessing radiochemical purity using radio-HPLC. Purification of [ ¹⁸ F]FSPG was conducted by trapping and washing of the radiotracer on Oasis MCX SPE cartridges, followed by a reverse elution of [ ¹⁸ F]FSPG in phosphate-buffered saline. Subsequently, the [ ¹⁸ F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.
Results: The optimized protocol produced [ ¹⁸ F]FSPG in 38.4 ± 2.6 % radiochemical yield and >96 % radiochemical purity with a molar activity of 11.1 ± 7.7 GBq/μmol. Small alterations, including the implementation of a reverse elution and an altered Hypercarb cartridge, led 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 [ ¹⁸ F]Fluoride.
Conclusions: We have developed a robust and facile method for [ ¹⁸ F]FSPG radiosynthesis in high radiotracer concentration, radiochemical yield, and radiochemical purity. This cassette-based method enabled the production of [ ¹⁸ F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of a cassette-based radiosynthesis on an automated synthesis module routinely used for clinical production makes the method amenable to rapid and widespread clinical translation.
(© 2021. The Author(s).)