神经炎症显像剂18F-PBR06的自动化制备  

Automated preparation of neuroinflammation imaging tracer F-PBR06

作　　者：乔洪文[1] 李则[1] 陈树安 梁志刚[1,2] 卢洁[1,3] QIAO Hongwen;LI Ze;CHEN Shu'an;LIANG Zhigang;LU Jie(Department of Nuclear Medicine,Xuanwu Hospital Capital Medical University,Beijing 100053,China;Information Center,Xuanwu Hospital Capital Medical University,Beijing 100053,China;Department of Radiology,Xuanwu Hospital Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院核医学科,北京100053 [2]首都医科大学宣武医院信息中心,北京100053 [3]首都医科大学宣武医院放射科,北京100053

出　　处：《核技术》2020年第8期66-73,共8页Nuclear Techniques

基　　金：国家自然科学基金(No.81701726);国家重点研发计划(No.2016YFC1306504、No.2017YFC0909100)资助。

摘　　要：18F-PBR06是一种二代18 kDa转位蛋白(18 kDa Translocator Protein,TSPO)靶向显像剂,主要用于神经炎症正电子发射断层成像(Positron Emission computed Tomography,PET)显像研究。为了推动该显像剂的应用,本研究基于Neptis Perform型放射性药物合成仪,开发了18F-PBR06自动化合成流程和一次性卡套;参考中国药典2015年版制定了产品质量标准,并进行了异常毒性检查;通过正常小鼠实验考察产品生物分布情况。基于以上内容,本研究开展了正常志愿者和多发性硬化患者18F-PBR06 PET显像预实验。结果表明:18F-PBR06制备放射化学产率为(32±5)%(经衰减校正,n=20),放化纯度大于99%,比活度大于111 GBq·μmol^-1,合成时间(54±2)min(n=20);产品质控和异常毒性检查均符合中国药典相关要求。18F-PBR06在小鼠肾、肺、脾和心脏等TSPO高表达器官摄取较高。预试验结果表明:多发硬化患者丘脑和脑桥的放射性摄取较正常人明显升高,这与该患者磁共振成像发现的病灶区域一致。以上结果证明本研究开发的工艺可以制备得到满足科研和临床应用要求的18F-PBR06制剂,为进一步神经炎症PET显像研究奠定了基础。[Background] The 18 kDa translocator protein(TSPO) is an important neuroinflammatory imaging target for neurological diseases.18F-PBR06 is a second-generation TSPO targeting agent with suitable biological properties, which has been used for human imaging. [Purpose] The study aims to promote the application of the imaging tracer 18F-PBR06 in research and clinical studies. [Methods] The disposable cassette system and process sequence for the Neptis Perform synthesizer was developed to produce 18F-PBR06. The quality control inspection method and specification for the product were established with reference to the Chinese Pharmacopoeia(2015 edition). The safety of the product was confirmed by the abnormal toxicity test following the requirements of the Chinese Pharmacopoeia(2015 edition). The biodistribution of the product was evaluated with normal mice. Based on the above research, the preliminary study of 18F-PBR06 PET imaging on healthy controls and patients with multiple sclerosis was performed. [Results]18F-PBR06 is successfully prepared with a radiochemical yield of(32±5)%(decay corrected, n=20), radiochemical purity >99%, specific activity >111 GBq·μmol^-1, and total time is(54±2) min(n=20). The product quality control tests and abnormal toxicity inspection are in compliance with the requirements of the Chinese Pharmacopoeia. The biodistribution study shows that high uptake is found in the organs of high densities of TSPO, including lung, kidney, spleen and heart. Preliminary PET/CT imaging research results show that the radioactive uptake in thalamus and pons of multiple sclerosis patient brain is significantly higher than that of health controls, and the white matter uptake is moderately increased. [Conclusions] The above results prove that 18F-PBR06 can be prepared through the process developed in this study. The product meets the requirements of research and clinical applications. This study makes favorable preparations for further clinical neuroinflammation PET imaging studies.

关 键 词：神经炎症 PET显像剂 18F-PBR06 自动化制备 多发性硬化 

分 类 号：TL923[核科学技术—核燃料循环与材料]