GMP-compliant automated radiosynthesis of [18F] SynVesT-1 for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)

Abstract

Background A novel positron emission tomography (PET) imaging tracer, [¹⁸F] SynVesT-1, targeting synaptic vesicle glycoprotein 2 (SV2A), has been developed to meet clinical demand. Utilizing the Trasis AllinOne-36 (AIO) module, we’ve automated synthesis to Good Manufacturing Practice (GMP) standards, ensuring sterile, pyrogen-free production. The fully GMP-compliant robust synthesis of [¹⁸F] SynVesT-1 boosting reliability and introducing a significant degree of simplicity and its comprehensive validation for routine human use. Results [¹⁸F] SynVesT-1 was synthesized by small modifications to the original [¹⁸F] SynVesT-1 synthesis protocol to better fit AIO module using an in-house designed cassette and sequence. With a relatively small precursor load of 5 mg, [¹⁸F] SynVesT-1 was obtained with consistently high radiochemical yields (RCY) of 20.6 ± 1.2% (the decay-corrected RCY, n = 3) at end of synthesis. Each of the final formulated batches demonstrated radiochemical purity (RCP) and enantiomeric purity surpassing 99%. The entire synthesis process was completed within a timeframe of 80 minutes (75 ± 3.1 min, n = 3), saves 11 minutes compared to reported GMP automated synthesis procedures. The in-human PET imaging of total body PET/CT and time-of-flight (TOF) PET/MR showed that [¹⁸F] SynVesT-1 is an excellent tracer for SV2A. It is advantageous for decentralized promotion and application in multi-center studies. Conclusion The use of AIO synthesizer maintains high production yields and increases reliability, reduces production time and allows rapid training of production staff. Besides, the as-prepared [¹⁸F] SynVesT-1 displays excellent in vivo binding properties in humans and holds great potential for the imaging and quantification of synaptic density in vivo.