Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2-¹⁸F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (¹⁸F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. ¹⁸F-FEA-Erlotinib was achieved within 50 min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50 GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of ¹⁸F-FEA-Erlotinib after incubated in PBS and FBS for 2 h. Cellular uptake and efflux experiment results indicated the specific binding of ¹⁸F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that ¹⁸F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of ¹⁸F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using ¹⁸F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients.

表皮生长因子受体（EGFR）作为治疗靶点已引起广泛关注。几种EGFR靶向药物（吉非替尼和厄洛替尼）已获得美国食品和药物管理局（FDA）的批准，并在临床治疗中获得了高度认可。然而，由于EGFR的表达和突变水平不同，这些药物在许多实体瘤中的疗效也各不相同。因此，已经开发了几种PET放射性示踪剂，用于选择性治疗对接受酪氨酸激酶抑制剂（TKI）治疗的PET / CT成像的反应性患者。在这项研究中，一种新型的氟18标记的4-苯胺基喹唑啉基PET示踪剂，1 N-（3-（1-（2- ¹⁸ F-氟乙基）-1 H合成了-1,2,3-三唑-4（基）苯基）-6,7-双（2-甲氧基乙氧基）喹唑啉-4-胺（¹⁸ F-FEA-厄洛替尼），并在体外进行了生物学评估，体内。¹⁸ F-FEA-埃罗替尼在50分钟内达到了88％的放射化学产率（衰变校正的RCY），50 GBq /μmol以上的平均比活和99％的放射化学纯度。体外稳定性研究表明，在PBS和FBS中孵育2小时后，¹⁸ F-FEA-厄洛替尼没有分解。细胞摄取和外排实验结果表明¹⁸ F-FEA-埃罗替尼与EGFR外显子19缺失的HCC827细胞系具有特异性结合。在体内，生物分布研究表明¹⁸F-FEA-厄洛替尼通过肝胆和肾脏排泄均表现出快速的血液清除。在PET图像中可以看到具有不同EGFR表达和突变的HepG2，HCC827和A431肿瘤异种移植物中¹⁸ F-FEA-埃罗替尼的肿瘤摄取。我们的结果证明了使用¹⁸ F-FEA-厄洛替尼作为PET示踪剂筛选EGFR TKIs敏感患者的可行性。