Abstract
1081
Introduction: Human epidermal growth factor receptor 2 (HER2)-targeted radioligands have plaductionyed an important role in the diagnosis of gastric cancer. In this study, we developed an Al18F-labeled HER2 Affibody (ZHER2:V2) and evaluated the potential for gastric cancer imaging. Methods: After the HER2 affibody was synthesized, radiolabeling of the ligand was performed using NOTA as the chelating moiety. The radiochemical yield of the Al18F-NOTA-ZHER2:V2 was identified by the high-performance liquid chromatography (HPLC) and instant thin-layer chromatography (ITLC). Several conditions for the quality control of the labeling stability of Al18F-NOTA-ZHER2:V2were evaluated in both physiological saline and human serum. Tumor uptake was evaluated by in vitro uptake assay in NCI-N87 (HER2+) cell. Micro-PET imaging of Al18F-NOTA-ZHER2:V2 in mice bearing NCI-N87 xenografted tumors. In vivo saturation binding assays were performed by the blocking study. The HER2 levels of xenografts were determined using immunohistochemistry (IHC). Results: Al18F-NOTA-ZHER2:V2 can be efficiently prepared within 30min with a radiochemical purity of more than 95%. The stability of Al18F-NOTA-ZHER2:V2was good in both physiological saline and human serum. The radiolabeled agent displayed excellent HER2-binding specificity and affinity in vivo and can be specificall ingested by HER2+ gastric cancer cells. High-level accumulation of Al18F-NOTA-ZHER2:V2was observed in HER2+ xenografts confirmed by immunohistochemical evidence. The uptake of radiotracer at tumor sites in Al18F-NOTA-ZHER2:V2 imaging was significantly high. Conclusions: Al18F-NOTA-ZHER2:V2is a promising radiotracer for non-invasive in vivo detecting HER2 status with the advantages of convenient synthesis and favorable imaging capability. Al18F-NOTA-ZHER2:V2can be used for HER2-positive gastric cancer imaging as a novel 18F PET radiotracer. Acknowledgements This study was supported by funds from the National Natural Science Foundation of China (NSFC) project (NO. 81571702) and the Beijing-Tianjin-Hebei Basic Research Special Cooperation project (NO. H2018206600)