Development of a Fluorinated Analogue of Erlotinib for PET Imaging of EGFR Mutation-Positive NSCLC

PurposePositron emission tomography (PET) using [C-11]erlotinib identifies non-small cell lung carcinoma (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFR(m)). 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(m) NSCLC.Procedures6-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-18]FEE, was obtained in a two-step synthesis, and PET acquisitions were carried out following its injection to NSCLC tumor-bearing mice.ResultsIn vitro, 6-O-FEE had maintained the selectivity and potency of erlotinib to EGFR(m) NSCLC. In vivo, 6-O-[F-18]FEE accumulation in EGFR(m) tumors at 60min after injection was 2- and 3.3-fold higher than in erlotinib-resistant or erlotinib-insensitive tumors, respectively.Conclusions6-O-[F-18]FEE holds promise for imaging EGFR(m) NSCLC, warranting further investigation to fully explore its potential for stratifying NSCLC patients.