Nanfang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, Guangdong Province 510515, China.
Nanfang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, Guangdong Province 510515, China.
Bioorg Med Chem Lett. 2020 Jun 15;30(12):127200. doi: 10.1016/j.bmcl.2020.127200. Epub 2020 Apr 15.
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-[F]fluoroethoxy)ethyl 4-methylbenzenesulfonate ([F]FEM) as a positron emission tomography (PET) agent for tumor imaging. In this study, [F]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 [F]FEM was 1.44 ± 0.04. The probe demonstrated good stability in 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 [F]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 [F]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 [F]FEM is a promising probe for tumor PET imaging.
在 21 世纪，癌症的发病率和死亡率迅速上升，癌症是世界上最具挑战性的疾病之一。本研究旨在开发 2-(2-[F]氟乙氧基)乙基 4-甲基苯磺酸酯 ([F]FEM) 作为肿瘤成像的正电子发射断层扫描 (PET) 探针。在这项研究中，[F]FEM 的合成产率高（45.4±5.8%），放射性比活度高（超过 25GBq/μmol），放射化学纯度高（超过 99%）。[F]FEM 的辛醇/水分配系数为 1.44±0.04。该探针在体外（磷酸盐缓冲盐水 (PBS) 和小鼠血清 (MS)) 和对五种不同肿瘤细胞系（A549、PC-3、HCC827、U87 和 MDA-MB-231）的结合特异性表现出良好的稳定性。荷瘤小鼠的 PET 成像显示，[F]FEM 特异性地积聚在五种不同肿瘤细胞系的肿瘤部位。肿瘤与肌肉（T/M）的平均比值超过 2，最大 T/M 值约为 3.5。生物分布和动态 PET 成像显示，大多数探针被肝脏代谢，而一小部分被肾脏代谢。此外，动态脑图像和定量数据表明 [F]FEM 可以快速穿过血脑屏障 (BBB) 并迅速消退，这表明它可能是一种很有前途的脑肿瘤成像候选探针。研究结果表明，[F]FEM 是一种很有前途的肿瘤 PET 成像探针。
