Radiosynthesis and preclinical evaluation of [F]FEM as a potential novel PET probe for tumor imaging
Radiosynthesis and preclinical evaluation of [F]FEM as a potential novel PET probe for tumor imaging
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[F-18]FEM 作为肿瘤成像潜在新型 PET 探针的放射合成和临床前评估
DOI：
10.1016/j.bmcl.2020.127200
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发表时间：
2020
影响因子：
2.7
通讯作者：
Shun Huang
中科院分区：
文献类型：
--
作者：
Yanping Jiang;Wenlan Zhou;Kongzhen Hu;Yanjiang Han;Penghui Sun;Quanshi Wang;Guiping Li;Hubing Wu;Ganghua Tang;Shun Huang
进入世纪，癌症作为世界上最具挑战性的疾病之一，其发病率和死亡率迅速上升。本研究的目的是开发2-（2-[18 F]氟乙氧基）乙基4-甲基苯磺酸酯（[18 F] FEM）作为正电子发射断层扫描（PET）的肿瘤成像剂。在本研究中，[18 F] FEM具有良好的放化产率（45.4 ± 5.8%），高比放射性（超过25 GBq/μ mol）和值得称赞的放化纯度（超过99%）。[18 F] FEM的辛醇/水分配系数为1.44 ± 0.04。该探针在体外（磷酸盐缓冲液（PBS）和小鼠血清（MS））中表现出良好的稳定性，并且与五种不同的肿瘤细胞系（A549、PC-3、HCC 827、U87和MDA-MB-231）具有特异性结合。荷瘤小鼠的PET成像显示，[18 F] FEM特异性地积聚在五种不同肿瘤细胞系的肿瘤部位。平均肿瘤与肌肉（T/M）比值超过2，最大T/M值达到约3.5。生物分布和动态PET成像显示，大多数探针由肝脏代谢，而一小部分由肾脏代谢。动态脑成像和定量数据显示[18 F] FEM可以快速穿过血脑屏障（BBB）并快速淡出，提示它可能是一种有前途的脑肿瘤成像候选探针。结果表明，[18 F] FEM是一种很有前途的肿瘤PET成像探头。
In the 21st century, the incidence and mortality of cancer, one of the most challenging diseases in the world, have rapidly increased. The purpose of this study was to develop 2-(2-[18F]fluoroethoxy)ethyl 4-methylbenzenesulfonate ([18F]FEM) as a positron emission tomography (PET) agent for tumor imaging. In this study, [18F]FEM was synthesized with a good radiochemical yield (45.4 ± 5.8%), high specific radioactivity (over 25 GBq/μmol), and commendable radiochemical purity (over 99%). The octanol/water partition coefficient of [18F]FEM was 1.44 ± 0.04. The probe demonstrated good stabilityin vitro(phosphate-buffered saline (PBS) and mouse serum (MS)), and binding specificity to five different tumor cell lines (A549, PC-3, HCC827, U87, and MDA-MB-231). PET imaging of tumor-bearing mice showed that [18F]FEM specifically accumulated at the tumor site of the five different tumor cell lines. The average tumor-to-muscle (T/M) ratio was over 2, and the maximum T/M values reached about 3.5. The biodistribution and dynamic PET imaging showed that most probes were metabolized by the liver, whereas a small part was metabolized by the kidney. Moreover, dynamic brain images and quantitative data showed [18F]FEM can quickly cross the blood brain barrier (BBB) and quickly fade out, thereby suggesting it may be a promising candidate probe for the imaging of brain tumors. The presented results demonstrated that [18F]FEM is a promising probe for tumor PET imaging.