The final optimized sequence provided [ 18 F]FSPG in 25.5% non-decay corrected RCY in approximately 1 h, producing ~383 MBq of [ 18 F]FSPG from 1.5 GBq starting activity without the use of a hot cell. Whilst our work has focused on optimizing this process for preclinical studies, we anticipate only minor adaptation of the sequence being required for clinical translation. To our knowledge, this method is the first cassette based synthesis and purification of [ 18 F]FSPG, allowing for a 'plug and play' operation that is desirable for a GMP process. The [ 18 F]FSPG was produced here at concentrations and amounts greater than that required for a patient dose (300 MBq). This has particular relevance to a 'dose on demand' cyclotron, where the amount of produced [ 18 F]fluoride is in the range of 1-2 GBq . Additionally, the RCP of the produced [ 18 F]FSPG is markedly higher than those used in previous clinical trials (>90%) . This improvement in RCP compared to syntheses producing [ 18 F]FSPG for clinical application may be due to the absence of radiolysis. Further studies are required to understand the interplay between [ 18 F]FSPG radiochemical concentration and RCP, but this work provides tantalizing evidence that multiple patient doses of [ 18 F]FSPG can be prepared when high starting activities are used. Here, we have demonstrated how practical changes to an automated procedure can result in significant improvements in research output whilst maintaining the ease of cassette-based radiochemistry. Specifically, we have demonstrated how barriers to PET imaging research can be overcome when low levels of starting activity are available.