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

Abstract

N‐(2‐chloro‐5‐(S‐2‐[18F]fluoroethyl)thiophenyl)‐N'‐(3‐thiomethylphenyl)‐N'‐methylguanidine, ([18F]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 [18F]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 [18F]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.

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].…”