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Article Abstract
Purpose: (S)-4-(3-F-Fluoropropyl)-ʟ-Glutamic Acid ([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, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [F]FSPG production are required. Here, we report a cassette-based method to produce [F]FSPG at high radioactivity concentrations from low amounts of starting activity.
Procedures: An automated synthesis and purification of [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 [F]FSPG and by assessing radiochemical purity using radio-HPLC. Purification of [F]FSPG was conducted by trapping and washing of the radiotracer on Oasis MCX SPE cartridges, followed by a reverse elution of [F]FSPG in phosphate-buffered saline. Subsequently, the [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 [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 [F]Fluoride.
Conclusions: We have developed a robust and facile method for [F]FSPG radiosynthesis in high radiotracer concentration, radiochemical yield, and radiochemical purity. This cassette-based method enabled the production of [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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578107 | PMC |
| http://dx.doi.org/10.1007/s11307-021-01609-w | DOI Listing |
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Article Synopsis
- [F]FSPG PET/CT is a promising imaging technique that helps detect cancer by measuring system x transport activity and may also provide insights into glutathione production, a key antioxidant.
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