p-[18F]FSTC的合成和初步动物学评价

    Synthesis and Preliminary Biological Evaluation of p-[18F]FSTC

    • 摘要: 碳酸酐酶Ⅸ(CA Ⅸ)是一个非常有前景的肿瘤乏氧显像的靶点,而一些磺胺类化合物和CA Ⅸ有特异性结合。为研发一种用于CA Ⅸ 检测的特异性正电子发射断层显像(PET)探针,应用点击化学(click chemistry)方法快速高效地合成了对CA Ⅸ有特异性结合的含氟磺胺类化合物1-(2-[18F]氟乙基)-N-(4-磺酰胺基苯基)-1H-1,2,3-三氮唑-4-酰胺(p-[18F]FSTC),合成时间约60min,标记率为90%,标记物经高效液相分离后放化纯度大于98%。p-[18F]FSTC在体内外稳定,正常小鼠体内分布结果显示,在血液中的清除较慢,脾、肺、肾和胃中的摄取较高。本工作为进一步研究18F标记的磺胺类化合物作为一种肿瘤乏氧显像PET探针提供了实验依据。

       

      Abstract: Carbonic anhydrase Ⅸ (CA Ⅸ) is a promising target for tumor hypoxia imaging, and some sulfamide compounds can specifically bind to human CA Ⅸ. In order to explore a novel positron emission tomography(PET) probe for detecting CA Ⅸ, the 1-(2-[18F]fluoroethyl)-N-(4-sulfamoylphenyl)-1H-1, 2, 3-triazole-4-carboxamide(p-[18F]FSTC) which has specific binding affinity to CA Ⅸ was radio-synthesized fast and efficiently by a “click chemistry” method. The labeling efficiency of p-[18F]FSTC is 90% and the total synthesis time is about 60 min. The radiochemical purity of p-[18F]FSTC is over 98% after HPLC purification. The stability of p-[18F]FSTC both in vitro and in vivo is high. The biodistribution of p-[18F]FSTC in normal mice shows that the clearance of p-[18F]FSTC in the blood is very slow; the uptake in spleen, lung, kidney and stomach is high. These preliminary results provide some experimental basis for further study of fluorine-18 labeled sulfamide as PET probes for tumor hypoxia imaging.

       

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