Development of an automated, GMP compliant FASTlab™ radiosynthesis of [18 F]GE-179 for the clinical study of activated NMDA receptors

Abstract N ‐(2‐chloro‐5‐( S ‐2‐[ 18 F]fluoroethyl)thiophenyl)‐ N '‐(3‐thiomethylphenyl)‐ N '‐methylguanidine, ([ 18 F] GE‐179 ), has been identified as a promising positron emission tomography (PET) ligand for the intra‐channel phencyclidine (PCP) binding site of the N ‐methyl‐ D ‐aspartate (NMDA) receptor. The radiosynthesis of [ 18 F] GE‐179 has only been performed at low radioactivity levels. However, the manufacture of a GMP compliant product at high radioactivity levels was required for clinical studies. We describe the development of a process using the GE FASTlab™ radiosynthesis platform coupled with HPLC purification. The radiosynthesis is a two‐step process, involving the nucleophilic fluorination of ethylene ditosylate, 11 , followed by alkylation to the deprotonated thiol precursor, N ‐(2‐chloro‐5‐thiophenol)‐ N '‐(3‐thiomethylphenyl)‐ N '‐methyl guanidine, 8 . The crude product was purified by semi‐preparative HPLC to give the formulated product in an activity yield (AY) of 7 ± 2% ( n = 15) with a total synthesis time of 120 minutes. The radioactive concentration (RAC) and radiochemical purity (RCP) were 328 ± 77 MBq/mL and 96.5 ± 1% respectively and the total chemical content was 2 ± 1 μg. The final formulation volume was 14 mL. The previously described radiosynthesis of [ 18 F] GE‐179 was successfully modified to deliver an process on the FASTlab™ that allows the manufacture of a GMP quality product from high starting radioactivitity (up to 80 GBq) and delivers a product suitable for clinical use.