Si Tang1,2, XiaoChun Yang1,2, Chao Zhou1,2, Yan Mei1, JiaCong Ye1, XiaoFei Zhang1,2, GuoKai Feng1, WeiGuang Zhang3,4, Xu Zhang5,6, Wei Fan7,8. 1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. 2. Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. 3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. zhangwg@sysucc.org.cn. 4. Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. zhangwg@sysucc.org.cn. 5. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. zhangx2@sysucc.org.cn. 6. Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. zhangx2@sysucc.org.cn. 7. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. fanwei@sysucc.org.cn. 8. Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. fanwei@sysucc.org.cn.
Abstract
PURPOSE: Positron emission tomography (PET) imaging was not efficiently used in the early diagnosis of hepatocellular carcinoma (HCC) due to the lack of appropriate tracers. Sodium pump Na + /K + ATPase subunit α1 (NKAα1) emerges to be a potential diagnostic biomarker of HCC. Here, we investigated the feasibility of 18F-ALF-NOTA-S3, a PET tracer based on an NKAα1 peptide, to detect small HCC. PROCEDURES: GEPIA database was searched to obtain the expression characteristics of NKAα1 in HCC and its relationship with the prognosis. PET/CT was performed in orthotopic, diethylnitrosamine (DEN)-induced and genetically engineered HCC mouse models to evaluate the use of 18F-ALF-NOTA-S3 to detect HCC lesions. RESULTS: NKAα1 is overexpressed in early HCC with a high positive rate and may correlate with poor survival. In orthotopic, DEN-induced and genetically engineered HCC mouse models, PET/CT imaging showed a high accumulation of 18F-ALF-NOTA-S3 in the tumor. The tumor-to-liver ratios are 2.56 ± 1.02, 4.41 ± 1.09, and 4.59 ± 0.65, respectively. Upregulated NKAα1 expression in tumors were verified by immunohistochemistry. Furthermore, 18F-ALF-NOTA-S3 has the ability to detect small HCC lesions with diameters of 2-5 mm. CONCLUSIONS: NKAα1 may serve as a suitable diagnostic biomarker for HCC. 18F-ALF-NOTA-S3 shows great potential for PET imaging of HCC.
PURPOSE: Positron emission tomography (PET) imaging was not efficiently used in the early diagnosis of hepatocellular carcinoma (HCC) due to the lack of appropriate tracers. Sodium pump Na + /K + ATPase subunit α1 (NKAα1) emerges to be a potential diagnostic biomarker of HCC. Here, we investigated the feasibility of 18F-ALF-NOTA-S3, a PET tracer based on an NKAα1 peptide, to detect small HCC. PROCEDURES: GEPIA database was searched to obtain the expression characteristics of NKAα1 in HCC and its relationship with the prognosis. PET/CT was performed in orthotopic, diethylnitrosamine (DEN)-induced and genetically engineered HCC mouse models to evaluate the use of 18F-ALF-NOTA-S3 to detect HCC lesions. RESULTS: NKAα1 is overexpressed in early HCC with a high positive rate and may correlate with poor survival. In orthotopic, DEN-induced and genetically engineered HCC mouse models, PET/CT imaging showed a high accumulation of 18F-ALF-NOTA-S3 in the tumor. The tumor-to-liver ratios are 2.56 ± 1.02, 4.41 ± 1.09, and 4.59 ± 0.65, respectively. Upregulated NKAα1 expression in tumors were verified by immunohistochemistry. Furthermore, 18F-ALF-NOTA-S3 has the ability to detect small HCC lesions with diameters of 2-5 mm. CONCLUSIONS: NKAα1 may serve as a suitable diagnostic biomarker for HCC. 18F-ALF-NOTA-S3 shows great potential for PET imaging of HCC.
Authors: Tatjana Mijatovic; Eric Van Quaquebeke; Bruno Delest; Olivier Debeir; Francis Darro; Robert Kiss Journal: Biochim Biophys Acta Date: 2007-07-04