N-[¹⁸F]fluoroacetylcrizotinib, a fluorine-18 labeled derivative of the first FDA approved tyrosine kinase inhibitor (TKI) for the treatment of Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), crizotinib, was successfully synthesized for use in positron emission tomography (PET). Sequential in vitro biological evaluation of fluoracetylcrizotinib and in vivo biodistribution studies of [¹⁸F]fluoroacetylcrizotinib demonstrated that the biological activity of the parent compound remained unchanged, with potent ALK kinase inhibition and effective tumor growth inhibition. These results show that [¹⁸F]fluoroacetylcrizotinib has the potential to be a promising PET ligand for use in NSCLC imaging. The utility of PET in this context provides a non-invasive, quantifiable method to inform on the pharmacokinetics of an ALK-inhibitor such as crizotinib prior to a clinical trial, as well as during a trial in the event of acquired drug resistance.

N-[ ¹⁸ F] 氟乙酰克唑替尼是第一个 FDA 批准的酪氨酸激酶抑制剂 (TKI) 的氟 18 标记衍生物，用于治疗间变性淋巴瘤激酶 (ALK) 重排的非小细胞肺癌 (NSCLC)，克唑替尼，是成功合成用于正电子发射断层扫描 (PET)。氟乙酰克唑替尼的连续体外生物学评估和[ ¹⁸ F] 氟乙酰克唑替尼的体内生物分布研究表明，母体化合物的生物学活性保持不变，具有有效的 ALK 激酶抑制和有效的肿瘤生长抑制。这些结果表明 [ ¹⁸F]氟乙酰克唑替尼有可能成为用于非小细胞肺癌成像的有前途的 PET 配体。在这种情况下，PET 的效用提供了一种非侵入性的、可量化的方法，可以在临床试验之前以及在获得性耐药的情况下在试验期间了解 ALK 抑制剂（如克唑替尼）的药代动力学。