开发一种氟代埃罗替尼类似物，用于正电子发射断层扫描（PET）成像检测表皮生长因子受体（EGFR）突变阳性非小细胞肺癌。
Development of a Fluorinated Analogue of Erlotinib for PET Imaging of EGFR Mutation-Positive NSCLC.
机构信息
Cyclotron/Radiochemistry/MicroPET Unit, Hadassah Hebrew University Hospital, Hadassah Medical Organization, 91120, Jerusalem, Israel.
出版信息
Mol Imaging Biol. 2019 Aug;21(4):696-704. doi: 10.1007/s11307-018-1286-8.
PURPOSE
Positron emission tomography (PET) using [C]erlotinib identifies non-small cell lung carcinoma (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFR). The short half-life of C-11, however, limits its clinical utility to centers with a nearby cyclotron. We therefore developed a F-18-labeled analogue of erlotinib for imaging EGFR NSCLC.
PROCEDURES
6-O-Fluoroethylerlotinib (6-O-FEE) was synthesized and its anti-proliferative activity was tested using human NSCLC cell lines. The F-18-labeled compound, 6-O-[F]FEE, was obtained in a two-step synthesis, and PET acquisitions were carried out following its injection to NSCLC tumor-bearing mice.
RESULTS
In vitro, 6-O-FEE had maintained the selectivity and potency of erlotinib to EGFR NSCLC. In vivo, 6-O-[F]FEE accumulation in EGFR tumors at 60 min after injection was 2- and 3.3-fold higher than in erlotinib-resistant or erlotinib-insensitive tumors, respectively.
CONCLUSIONS
6-O-[F]FEE holds promise for imaging EGFR NSCLC, warranting further investigation to fully explore its potential for stratifying NSCLC patients.
目的
使用 [C] 厄洛替尼的正电子发射断层扫描（PET）可识别表皮生长因子受体（EGFR）中存在激活突变的非小细胞肺癌（NSCLC）肿瘤。然而，C-11 的半衰期较短，这将其临床应用限制在附近有回旋加速器的中心。因此，我们开发了一种用于成像 EGFR NSCLC 的 F-18 标记的厄洛替尼类似物。
方法
合成了 6-O-氟乙基厄洛替尼（6-O-FEE），并使用人非小细胞肺癌细胞系测试了其抗增殖活性。F-18 标记的化合物 6-O-[F]FEE 通过两步合成获得，在向 NSCLC 荷瘤小鼠注射后进行 PET 采集。
结果
在体外，6-O-FEE 保持了厄洛替尼对 EGFR NSCLC 的选择性和效力。在体内，注射后 60 分钟，6-O-[F]FEE 在 EGFR 肿瘤中的积累分别比厄洛替尼耐药或不敏感的肿瘤高 2 倍和 3.3 倍。
结论
6-O-[F]FEE 有望用于成像 EGFR NSCLC，值得进一步研究以充分探索其在分层 NSCLC 患者中的潜力。
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