Aβ显像剂^(18)F-AV45的自动化合成及临床验证

Automated Synthesis of^(18)F-AV45 for Aβ-Amyloid Imaging and its Preliminary Clinical Application

使用进口氟多功能合成模块TRACERlab FX2 N合成器自动化合成β-淀粉样蛋白(β-amyloid protein,Aβ)正电子显像剂^(18)F-AV45,并进行临床验证。在TRACERlab FX2 N合成器上,以AV105为前体,与^(18)F-发生亲核反应后,依次经酸水解及碱中和,经过高效液相色谱法(high performance liquid chromatography,HPLC)分离并纯化后获得^(18)F-AV45,进行质量控制。并用制备的^(18)F-AV45对1例阿尔兹海默病(Alzheimer disease,AD)患者及1例健康对照者行^(18)F-AV45 PET/CT扫描。结果表明,^(18)F-AV45合成时间为80 min,不校正合成效率为(17.02±1.52)%(n=6),产品放化纯度大于95%。临床应用显示^(18)F-AV45在AD患者大脑皮层摄取弥漫增高,提示大脑皮层β淀粉样蛋白沉积;在健康对照者大脑皮层未见明显摄取,即大脑皮层未见β淀粉样蛋白沉积。TRACERlab FX2 N合成器自动化合成^(18)F-AV45简便快捷,重复性好,制备出的^(18)F-AV45产品质量符合临床要求,该合成方法可为^(18)F-AV45模块合成提供参考。

Aβ-Amyloid positron imaging agent^(18)F-AV45 was synthesized automatically using TRACERlab FX2 N radiosynthesis module and the clinical imaging of^(18)F-AV45 was evaluated.AV105 was used as the precursor,which reacted with^(18)F ion at 130℃for 10 minutes on the TRACERlab FX2 N,followed by acid hydrolysis and neutralization with NaOH,and then the reaction mixture was separated by high-performance liquid chromatography(HPLC)method to obtain the target compound^(18)F-AV45,which was next purified by solid-phase extraction method.The HPLC quality control analysis of the final^(18)F-AV45 injection was carried out.The radiochemical purity of^(18)F-AV45 was determined using a HPLC system equipped with a C18 column(InfinityLab Poroshell 120 EC-C1,4μm,4.6 mm×100 mm)which was eluted with a mobile phase of acetonitrile/20 mM ammonium acetate(40∶60,v/v)at a flow rate of 1 mL/min.The absorbance of 350 nm and the radioactivity in the eluate flow were monitored with a diode array detector and a flow count detector,respectively.One case of patients with Alzheimer’s disease(AD)and one healthy person underwent^(18)F-AV45 PET/CT scanning.The results showed that it took 80 minutes from^(18)F ion to^(18)F-AV45,no-corrected efficiency was(17.02±1.52)%(n=6),radiochemistry purity was over 95%.The results of PET imaging showed that^(18)F-AV45 uptake was diffusely increased in the cerebral cortex of patient with AD,which indicated deposition of amyloid beta protein in cerebral cortex.And the results of imaging of the healthy person showed^(18)F-AV45 was no obvious uptake in cerebral cortex,namely,there was no deposition of amyloid beta protein in cerebral cortex.^(18)F-AV45 could be synthesized automatically and simply by TRACERlab FX2 N with good repeatability.The quality of^(18)F-AV45 injection meets the requirements for clinical use.In addition,^(18)F-AV45 has clinical application value in the diagnosis of patients with AD.