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

Abstract

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 using 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 radio-HPLC. Purification of [18F]FSPG was conducted by trapping and washing of the radiotracer on Oasis MCX SPE cartridges, 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 % 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 [18F]Fluoride. Conclusions We have developed a robust and facile method for [18F]FSPG radiosynthesis in high radiotracer concentration, radiochemical yield, and radiochemical purity. 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 a cassette-based radiosynthesis on an automated synthesis module routinely used for clinical production makes the method amenable to rapid and widespread clinical translation.

Automated Radiosynthesis, Preliminary In Vitro/In Vivo Characterization of OncoFAP-Based Radiopharmaceuticals for Cancer Imaging and Therapy

“…The procedures described in this article are easy to implement, safe and robust. We based these procedures on the FASTLab automated module, a radiolabeling platform already broadly applied to produce other radiopharmaceuticals at the commercial scale [27][28][29]. With the aim to enable production of [ 68 Ga]-DOTAGA/NODAGA-OncoFAP radiopharmaceuticals also in small radiopharmacy sites with limited financial resources, we have also generated a radiolabeling single-vial cold kit.…”

Automated radiolabelling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging and therapy

“…Methodologies described here are novel, easy to implement, safe and robust. We based these procedures on the FASTLab2 automated module, a radiolabelling platform already broadly applied to produce other radiopharmaceuticals at the commercial scale [21][22][23].…”

Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system xC- in tumors

“…[ 18 F]FRPG and [ 18 F]FSPG were synthesized from their corresponding naphthalenesulfonyl precursors (Life Molecular Imaging) using a GE FASTlab automated synthesis module using a previously reported method 43 . The analysis and identification of [ 18 F]FRPG and [ 18 F]FSPG was also conducted as reported previously 43 .…”

“…[ 18 F]FRPG and [ 18 F]FSPG were synthesized from their corresponding naphthalenesulfonyl precursors (Life Molecular Imaging) using a GE FASTlab automated synthesis module using a previously reported method 43 . The analysis and identification of [ 18 F]FRPG and [ 18 F]FSPG was also conducted as reported previously 43 . For a detailed description of precursor and 19 F reference standard syntheses, along with their corresponding spectra, see Supplementary Information : Synthesis and Spectra .…”