Targeting Phosphatidylethanolamine with Fluorine-18 Labeled Small Molecule Probe for Apoptosis Imaging
Molecular Imaging and Biology(2019)
摘要
Purpose 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. Procedure In this study, we have radiolabeled PE-binding polypeptide duramycin with fluorine-18 for PET imaging of apoptosis. Al[ 18 F]F-NOTA-PEG 3 -duramycin was synthesized via chelation reaction of NOTA-PEG 3 -duramycin with Al[ 18 F]F. PE-binding capacity of Al[ 18 F]F-NOTA-PEG 3 -duramycin was determined in a competitive radiometric PE-binding assay. The pharmacokinetic profile was evaluated in Kunming mice. The apoptosis imaging capacity of Al[ 18 F]F-NOTA-PEG 3 -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. Results 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[ 18 F]F-NOTA-PEG 3 -duramycin with camptothecin-induced apoptotic cells resulted in a tripling increase. A competitive radiometric PE-binding assay strongly confirmed the binding of Al[ 18 F]F-NOTA-PEG 3 -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[ 18 F]F-NOTA-PEG 3 -duramycin demonstrated 2-fold increase in erlotinib-treated HCC827 tumors in nude mice. Conclusion Considering the facile preparation and improved biological properties, Al[ 18 F]F-NOTA-PEG 3 -duramycin seems to be a promising PET tracer candidate for imaging apoptosis in the monitoring of cancer treatment.
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关键词
Cell death, Positron emission tomography, Al[18F]F, Therapy evaluation
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