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. 2020 Apr;63(4):183-195.
doi: 10.1002/jlcr.3831. Epub 2020 Mar 5.

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

Imtiaz Khan  1 , Tom Christian Berg  2 , Jane Brown  1 , Rajiv Bhalla  1 , Anthony Wilson  1 , Andrew Black  1 , Graeme McRobbie  1 , James Nairne  1 , Andreas Olsson  2 , William Trigg  1
Affiliations

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

Imtiaz Khan et al. J Labelled Comp Radiopharm. 2020 Apr.

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.

Keywords: 2-[18F]fluoroethyl tosylate; FASTlabTM, N-Methyl-D-aspartate (NMDA) receptor, GMP.; GE-179; PET; alkylation; automation.

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References

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