PET probe detecting non-small cell lung cancer susceptible to epidermal growth factor receptor tyrosine kinase inhibitor therapy
PET probe detecting non-small cell lung cancer susceptible to epidermal growth factor receptor tyrosine kinase inhibitor therapy
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PET探针检测对表皮生长因子受体酪氨酸激酶抑制剂治疗敏感的非小细胞肺癌
DOI：
10.1016/j.bmc.2018.02.007
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hideo Saji
中科院分区：
文献类型：
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作者：
Akira Makino ;Anna Miyazaki ;Ayaka Tomoike ;Hiroyuki Kimura ;Kenji Arimitsu ;Masahiko Hirata ;Yoshiro Ohmomo ;Ryuichi Nishii ;Hidehiko Okazawa ;Yasushi Kiyono ;Masahiro Ono ;Hideo Saji
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）用作非小细胞肺癌（NSCLC）患者的分子靶向治疗。该疗法适用于EGFR初次突变L858R，但一年半内出现EGFR二次突变引起的耐药性的患者。为了通过正电子发射断层扫描（PET）成像无创检测EGFR-TKIs治疗阳性患者，新合成了氟18标记的噻吩并嘧啶衍生物[18F]FTP2。 EGFR 抑制测定、细胞摄取研究和阻断研究表明[18F]FTP2 以高选择性亲和力与具有 L858R 突变的 EGFR 结合，而不是与 L858R/T790M 双突变的 EGFR 结合。在使用荷瘤小鼠的动物 PET 研究中，表达 L858R 突变 EGFR 的 H3255 细胞比表达 L858R/T790M 双突变 EGFR 的 H1975 细胞更清晰可见。[18F]FTP2 具有检测对 EGFR-TKI 治疗敏感的 NSCLC 的潜力。
Tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR-TKIs) are used as molecular targeted therapy for non-small cell lung cancer (NSCLC) patients. The therapy is applied to the patients having EGFR-primary L858R mutation, but drug tolerance caused by EGFR-secondary mutation is occurred within one and half years. For the non-invasive detection of the EGFR-TKIs treatment positive patients by positron emission tomograpy (PET) imagaing, fluorine-18 labeled thienopyrimidine derivative,[18F]FTP2was newly synthesized. EGFR inhibition assay, cell uptake study, and blocking study indicated[18F]FTP2binds with high and selective affinity for EGFR with L858R mutation, and not with L858R/T790M dual mutations. On animal PET study using tumor bearing mice, H3255 cells expressing L858R mutated EGFR was more clearly visualized than H1975 cells expressing L858R/T790M dual mutated EGFR.[18F]FTP2has potential for detecting NSCLC which is susceptible to EGFR-TKI treatment.