Externalization of phosphatidylethanolamine (PE) in dying cells makes the phospholipid an attractive target for apoptosis imaging. However, no ideal PE-targeted positron emission tomography (PET) radiotracer was developed. The goal of the study was to develop a novel PE-targeted radiopharmaceutical to imaging apoptosis.In this study, we have radiolabeled PE-binding polypeptide duramycin with fluorine-18 for PET imaging of apoptosis. Al[18F]F-NOTA-PEG3-duramycin was synthesized via chelation reaction of NOTA-PEG3-duramycin with Al[18F]F. PE-binding capacity of Al[18F]F-NOTA-PEG3-duramycin was determined in a competitive radiometric PE-binding assay. The pharmacokinetic profile was evaluated in Kunming mice. The apoptosis imaging capacity of Al[18F]F-NOTA-PEG3-duramycin was evaluated using in vitro cell uptake assay with camptothecin-treated Jurkat cells, along with in vivo PET imaging using erlotinib-treated nude mice.The total synthesis procedure lasted for 30 min, with a decay-uncorrected radiochemical yield of 21.3 ± 2.6 % (n = 10). Compared with the control cells, the binding of Al[18F]F-NOTA-PEG3-duramycin with camptothecin-induced apoptotic cells resulted in a tripling increase. A competitive radiometric PE-binding assay strongly confirmed the binding of Al[18F]F-NOTA-PEG3-duramycin to PE. The biodistribution study showed rapid blood clearance, prominent kidney retention, and low liver uptake. In the in vivo PET/CT imaging, Al[18F]F-NOTA-PEG3-duramycin demonstrated 2-fold increase in erlotinib-treated HCC827 tumors in nude mice.Considering the facile preparation and improved biological properties, Al[18F]F-NOTA-PEG3-duramycin seems to be a promising PET tracer candidate for imaging apoptosis in the monitoring of cancer treatment.