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

Purpose Positron emission tomography (PET) using [ 11 C]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. 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-[ 18 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 m NSCLC. In vivo , 6-O-[ 18 F]FEE accumulation in EGFR m 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-[ 18 F]FEE holds promise for imaging EGFR m NSCLC, warranting further investigation to fully explore its potential for stratifying NSCLC patients.