Ofer Shamni1, Hilbert Grievink1, Batel Itamar1, Eyal Mishani1, Galith Abourbeh2. 1. Cyclotron/Radiochemistry/MicroPET Unit, Hadassah Hebrew University Hospital, Hadassah Medical Organization, 91120, Jerusalem, Israel. 2. Cyclotron/Radiochemistry/MicroPET Unit, Hadassah Hebrew University Hospital, Hadassah Medical Organization, 91120, Jerusalem, Israel. abourbehg@hadassah.org.il.
Abstract
PURPOSE: Positron 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. 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-[18F]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 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. CONCLUSIONS: 6-O-[18F]FEE holds promise for imaging EGFRm NSCLC, warranting further investigation to fully explore its potential for stratifying NSCLC patients.
PURPOSE: Positron 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. PROCEDURES: 6-O-Fluoroethylerlotinib (6-O-FEE) was synthesized and its anti-proliferative activity was tested using humanNSCLC 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. RESULTS: In 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. CONCLUSIONS: 6-O-[18F]FEE holds promise for imaging EGFRm NSCLC, warranting further investigation to fully explore its potential for stratifying NSCLCpatients.
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