PET probe detecting non-small cell lung cancer susceptible to epidermal growth factor receptor tyrosine kinase inhibitor therapy

Publication date: 1 May 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 8
Author(s): Akira Makino, Anna Miyazaki, Ayaka Tomoike, Hiroyuki Kimura, Kenji Arimitsu, Masahiko Hirata, Yoshiro Ohmomo, Ryuichi Nishii, Hidehiko Okazawa, Yasushi Kiyono, Masahiro Ono, Hideo Saji
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]FTP2 was newly synthesized. EGFR inhibition assay, cell uptake study, and blocking study indicated [¹⁸F]FTP2 binds 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]FTP2 has potential for detecting NSCLC which is susceptible to EGFR-TKI treatment.

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