The tyrosine kinase MET (hepatocyte growth factor receptor) is activated or mutated in a wide range of cancers and is often correlated with a poor prognosis. Precision medicine with positron emission tomography (PET) can potentially aid in the assessment of tumor biochemistry and heterogeneity, which can prompt the selection of the most effective therapeutic regimes. The selective MET inhibitor PF04217903 (1) formed the basis for a bioisosteric replacement, leading to the deoxyfluorinated analog [¹⁸F]2. [¹⁸F]2 could be synthesized with a “hydrous fluoroethylation” protocol in 6.3 ± 2.6% radiochemical yield and a molar activity of >50 GBq/μmol. In vitro autoradiography indicated that [¹⁸F]2 selectively binds to MET in PC3 tumor tissue, and in vivo biodistribution in mice showed predominantly a hepatobiliary excretion along with a low retention of radiotracer in other organs.

中文翻译：

---

选择性 MET 激酶正电子发射断层扫描示踪剂的合成和临床前评价


酪氨酸激酶 MET（肝细胞生长因子受体）在多种癌症中被激活或突变，并且通常与不良预后相关。正电子发射断层扫描 (PET) 的精准医学可能有助于评估肿瘤生物化学和异质性，从而促进选择最有效的治疗方案。选择性 MET 抑制剂 PF04217903 (1) 形成了生物等排替代的基础，从而产生了脱氧氟化类似物 [ ¹⁸ F]2。 [ ¹⁸ F]2 可以通过“水合氟乙基化”方案合成，放射化学产率为 6.3 ± 2.6%，摩尔活性 >50 GBq/μmol。体外放射自显影表明，[ ¹⁸ F]2 选择性地与 PC3 肿瘤组织中的 MET 结合，并且小鼠体内的生物分布主要显示出肝胆排泄，而放射性示踪剂在其他器官中的保留量较低。