Radiosynthesis and Analysis of (S)-4-(3-[ 18 F]Fluoropropyl)-L-Glutamic Acid.

PURPOSE: (S)-4-(3-[18 F]Fluoropropyl)-L-glutamic acid ([18 F]FSPG) is an L-glutamate derivative used as a PET biomarker to assess intracellular redox status in vivo through targeting of the cystine/glutamate antiporter protein, xc - transporter. In this report, we describe a radiosynthesis of [18 F]FSPG for use in PET studies that address specific challenges in relation to the radiotracer purity, molar activity, and quality control testing methods.

PROCEDURES: The radiosynthesis of [18 F]FSPG was performed using a customised RNPlus Research automated radiosynthesis system (Synthra GmbH, Hamburg, Germany). [18 F]FSPG was labelled in the 3-fluoropropylmoiety at the 4-position of the glutamic acid backbone with fluorine-18 via substitution of nucleophilic [18 F]fluoride with a protected naphthylsulfonyloxy-propyl-L-glutamate derivative. Radiochemical purity of the final product was determined by radio HPLC using a new method of direct analysis using a Hypercarb C18 column.

RESULTS: The average radioactivity yield of [18 F]FSPG was 4.2 GBq (range, 3.4-4.8 GBq) at the end of synthesis, starting from 16 GBq of [18 F]fluoride at the end of bombardment (n = 10) in a synthesis time of 50 min. The average molar activity and radioactivity volumetric concentration at the end of synthesis were 66 GBq µmol-1 (range, 48-73 GBq µmol-1 ) and 343-400 MBq mL-1 , respectively.

CONCLUSION: Stability tests using a 4.6 GBq dose with a radioactivity volumetric concentration of 369 MBq mL-1 at the end of synthesis showed no observable radiolysis 3 h after production. The formulated product is of high radiochemical purity (> 95%) and higher molar activity compared to previous methods and is safe to inject into mice up to 3 h after production.