Journal of Isotopes ›› 2021, Vol. 34 ›› Issue (4): 370-380.DOI: 10.7538/tws.2020.youxian.070

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Synthesis and Preliminary Biological Evaluation of 18F Labeled Styryl Pyrimidine Derivatives as Aβ-Imaging Agents for Alzheimer’s Disease

LI Zhongyong;SHEN Langtao;QIAO Laicheng;WANG Chengzhi;LIANG Wei;SHEN Chen;CUI Haiping   

  1. Atom High Tech Co., Ltd., Beijing 102413, China;China Institute of Atomic Energy, Beijing 102413, China
  • Online:2021-08-20 Published:2021-08-20



  1. 原子高科股份有限公司,北京102413;中国原子能科学研究院,北京102413

Abstract: Two styryl pyrimidine derivatives substituted by p-tosyloxymethyl, Boc-SPm2-OTs and Boc-SPm5-OTs, were designed and successful synthesized, which were labeled by 18F to prepared 18F-SPm2 and 18F-SPm5 by nucleophilic substitution. The radiochemical purities of both 18F-SPm2 and 18F-SPm5 were more than 99%. Both 18F-SPm2 and 18F-SPm5 had ideal lipophilicity (LogP=1-2.5) and can maintaining stability in normal saline for over 3 h and can bind to Aβ selectively, but both 18F-SPm2 and 18F-SPm5 displayed less binding affinity (the Ki values were 246.6 nmol/L and 318.2 nmol/L, respectively). The results of biodistribution in mice demonstrated that both 18F-SPm2 and 18F-SPm5 showed relatively high initial brain uptake, with slow washout from normal brain and obvious defluorination in vivo. In conclusion, both 18F-SPm2 and 18F-SPm5 might not be ideal Aβ imaging agents, and further modifications were needed to improve the disadvantages.

Key words: alzheimer’s disease (AD), positron emission tomography (PET), β-Amyloid (Aβ), styryl pyrimidine derivatives

摘要: 为研发新型Aβ正电子显像剂,设计合成对甲苯磺酰氧基取代的苯乙烯基嘧啶化合物Boc-SPm2-OTs和Boc-SPm5-OTs,并通过亲核取代反应进行18F标记,得到18F-SPm2和18F-SPm5,放化纯度均大于99%。18F-SPm2和18F-SPm5均具有适宜的亲脂性(LogP=1~2.5),在生理盐水中可稳定存在3 h以上,能选择性结合Aβ,但其亲和性较弱(Ki分别为246.6 nmol/L和318.2 nmol/L),体内生物分布实验表明,两者初始脑放射性摄取均相对较高,但正常脑组织清除较慢,而且存在明显脱氟现象。初步的研究结果表明,18F-SPm2和18F-SPm5不是理想的Aβ显像剂,需要进行进一步的结构修饰以克服其缺点。

关键词: 阿兹海默病(AD), 正电子发射断层显像(PET), β淀粉样蛋白(Aβ), 苯乙烯基嘧啶化合物