^(18)F标记的苯乙烯基嘧啶类Aβ显像剂的制备与初步生物评价  

Synthesis and Preliminary Biological Evaluation of^(18)F Labeled Styryl Pyrimidine Derivatives as AβImaging Agents for Alzheimer’s Disease

作　　者：李忠勇 沈浪涛[1,2] 乔来成 王成志[1] 梁巍 沈忱 崔海平 LI Zhongyong;SHEN Langtao;QIAO Laicheng;WANG Chengzhi;LIANG Wei;SHEN Chen;CUI Haiping(Atom High Tech Co.,Ltd.,Beijing 102413,China;China Institute of Atomic Energy,Beijing 102413,China)

机构地区：[1]原子高科股份有限公司,北京102413 [2]中国原子能科学研究院,北京102413

出　　处：《同位素》2021年第4期370-380,I0003,共12页Journal of Isotopes

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^(18)F标记,得到^(18)F-SPm2和^(18)F-SPm5,放化纯度均大于99%。^(18)F-SPm2和^(18)F-SPm5均具有适宜的亲脂性(Log P=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(K_(i)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,^(18)F-SPm2和^(18)F-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。Two styryl pyrimidine derivatives substituted by p-tosyloxymethyl,Boc-SPm2-OTs and Boc-SPm5-OTs,were designed and successful synthesized,which were labeled by^(18)F to prepared^(18)F-SPm2 and^(18)F-SPm5 by nucleophilic substitution.The radiochemical purities of both^(18)F-SPm2 and^(18)F-SPm5 were more than 99%.Both^(18)F-SPm2 and^(18)F-SPm5 had ideal lipophilicity(Log P=1-2.5)and can maintaining stability in normal saline for over 3 h and can bind to Aβselectively,but both^(18)F-SPm2 and^(18)F-SPm5 displayed less binding affinity(the K_(i)values were 246.6 nmol/L and 318.2 nmol/L,respectively).The results of biodistribution in mice demonstrated that both^(18)F-SPm2 and^(18)F-SPm5 showed relatively high initial brain uptake,with slow washout from normal brain and obvious defluorination in vivo.In conclusion,both^(18)F-SPm2 and^(18)F-SPm5 might not be ideal Aβimaging agents,and further modifications were needed to improve the disadvantages.

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 

分 类 号：TL923[核科学技术—核燃料循环与材料] R817.9[医药卫生—影像医学与核医学]