The tyrosine kinase MET (hepatocyte growth factor receptor) is abnormally activated 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 to the deoxyfluorinated analogue [18F]2, intended as a PET tracer for MET. [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 specifically 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：

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选择性MET PET示踪剂[18F] PF04217903的合成和临床前评价

酪氨酸激酶MET（肝细胞生长因子受体）在多种癌症中均被异常激活，通常与不良预后相关。带有正电子发射断层扫描（PET）的精密医学可以潜在地帮助评估肿瘤的生物化学和异质性，从而可以促使人们选择最有效的治疗方案。选择性MET抑制剂PF04217903（1）为脱氧氟代类似物[18F] 2的生物立体替代提供了基础，后者用作MET的PET示踪剂。[18F] 2可以通过“含水氟乙基化”方案合成，放射化学产率为6.3±2.6％，摩尔活性> 50 GBq / µmol。体外放射自显影显示[18F] 2与PC3肿瘤组织中的MET特异性结合，