Abstract
PurposePositron emission tomography (PET) using [11C]erlotinib identifies non-small cell lung carcinoma (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFRm). 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 EGFRm 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-[18F]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 EGFRm NSCLC. In vivo, 6-O-[18F]FEE accumulation in EGFRm tumors at 60 min after injection was 2- and 3.3-fold higher than in erlotinib-resistant or erlotinib-insensitive tumors, respectively.Conclusions6-O-[18F]FEE holds promise for imaging EGFRm NSCLC, warranting further investigation to fully explore its potential for stratifying NSCLC patients.
Highlights
The epidermal growth factor receptor (EGFR) is overexpressed in over 60 % of non-small cell lung carcinoma (NSCLC) tumors, and its mutational status in advanced/ metastatic NSCLC has both a prognostic value and a therapeutic impact [1,2,3,4,5]
Optimal first-line treatment of EGFR mutation– positive (EGFRm) NSCLC comprises any of the approved EGFR tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and afatinib [6, 7, 10, 11]
NSCLC patients whose tumors do not harbor sensitizing EGFR mutations do not benefit from EGFR TKI therapy and should be treated with chemotherapy, specific inhibitors of other oncoproteins, or immune checkpoint inhibitors [6, 10, 11, 13]
Summary
The epidermal growth factor receptor (EGFR) is overexpressed in over 60 % of non-small cell lung carcinoma (NSCLC) tumors, and its mutational status in advanced/ metastatic NSCLC has both a prognostic value and a therapeutic impact [1,2,3,4,5]. The third-generation EGFR TKI, osimertinib, has been approved for the first-line treatment of EGFRm NSCLC [12]. These EGFR TKIs offer a longer progression-free survival (PFS), higher response rate (RR), and reduced side effects, compared to standard chemotherapy [6, 7]. NSCLC patients whose tumors do not harbor sensitizing EGFR mutations do not benefit from EGFR TKI therapy and should be treated with chemotherapy, specific inhibitors of other oncoproteins, or immune checkpoint inhibitors [6, 10, 11, 13].
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