Chen Lijuan, Li Xiaochen, Ge Yao, Li Huiqiang, Li Ruili, Song Xiaosheng, Liang Jianfei, Zhang Weifeng, Li Xiaona, Wang Xiaoqi, Wang Yunjuan, Wu Yaping, Bai Yan, Wang Meiyun
Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
School of Clinical Medicine, Henan University, Kaifeng, 475004, China.
EJNMMI Radiopharm Chem. 2024 Sep 10;9(1):66. doi: 10.1186/s41181-024-00284-w.
A novel positron emission tomography (PET) imaging tracer, [F] 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 [F] SynVesT-1 boosting reliability and introducing a significant degree of simplicity and its comprehensive validation for routine human use.
[F] SynVesT-1 was synthesized by small modifications to the original [F] 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, [F] 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 min (75 ± 3.1 min, n = 3), saves 11 min 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 [F] SynVesT-1 is an excellent tracer for SV2A. It is advantageous for decentralized promotion and application in multi-center studies.
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 [F] SynVesT-1 displays excellent in vivo binding properties in humans and holds great potential for the imaging and quantification of synaptic density in vivo.
为满足临床需求，已研发出一种新型正电子发射断层扫描（PET）成像示踪剂[F]SynVesT-1，其靶向突触囊泡糖蛋白2（SV2A）。利用Trasis AllinOne-36（AIO）模块，我们已将合成自动化至符合药品生产质量管理规范（GMP）标准，确保无菌、无热原生产。[F]SynVesT-1完全符合GMP的稳健合成提高了可靠性，并引入了显著的简便性及其用于常规人体使用的全面验证。
通过对原始[F]SynVesT-1合成方案进行微小修改来合成[F]SynVesT-1，以更好地适配使用内部设计的盒式装置和序列的AIO模块。在前体负载量相对较小为5 mg的情况下，合成结束时[F]SynVesT-1的放射性化学产率（RCY）始终保持在较高水平，为20.6±1.2%（经衰变校正的RCY，n = 3）。最终配制的每一批次均显示放射性化学纯度（RCP）和对映体纯度超过99%。整个合成过程在80分钟内完成（75±3.1分钟，n = 3），与已报道的GMP自动化合成程序相比节省了11分钟。全身PET/CT和飞行时间（TOF）PET/MR的人体PET成像显示，[F]SynVesT-1是一种用于SV2A的优秀示踪剂。它有利于在多中心研究中进行分散推广和应用。
使用AIO合成器可保持高产量并提高可靠性，减少生产时间，并能快速培训生产人员。此外，所制备的[F]SynVesT-1在人体中显示出优异的体内结合特性，在体内突触密度成像和定量方面具有巨大潜力。
