Implementation of a reverse elution, an improved remote collection, and alteration of the commercially-available hypercarb cartridge used for the solid phase purification of the radiotracer resulted in a considerable improvement in radiotracer concentration and RCY. This optimized protocol reliably produced [ 18 F]FSPG at high concentrations, allowing for large-scale in vivo studies and transportation to other sites despite low levels of starting radioactivity. The optimized protocol will increase accessibility to [ 18 F]FSPG and is well-placed for clinical translation. a The synthesis was performed using cassette layout presented in Fig. . All other entries were performed according to the layout in Fig. . b Values in parentheses refer to the volume transferred to the reactor. c The product was eluted from the MCX cartridges manually after failing to elute during the automated synthesis. d Syringe speed increased 2.5 fold to 17.5 mL/min.