本课题组研发的氟标谷氨酸(18F-FPGLU)是有重要临床应用前景的肿瘤PET显像剂。前期研究发现其在肿瘤中的摄取与兴奋性谷氨酸转运系统XAG-有关，但其具体的转运分子机制不明。预实验研究发现其在肺腺癌细胞中转运除与兴奋性谷氨酸转运体EAAC1密切相关外，可能还存在其他转运机制，而且肺腺癌中另外两个兴奋性谷氨酸转运体GLAST和GLT-1表达较正常肺组织明显上调。在此基础上，我们提出GLAST/GLT-1转运体是肿瘤细胞浓聚谷氨酸类PET显像剂重要分子机制，是研制谷氨酸类PET显像剂的重要靶点的假说。本项目拟分别建立过表达和基因干扰下调GLAST\GLT-1表达的肿瘤细胞株和荷瘤裸鼠模型，研究肿瘤细胞GLAST\GLT-1表达与18F-FPGLU摄取的相关性，明确肿瘤细胞浓聚18F-FPGLU的分子机制，为其应用于临床肿瘤显像提供重要理论基础，为肿瘤谷氨酸类PET显像剂的研制提供新的靶点。

N-(2-18F-Fluoropropionyl)-L-glutamate (18F-FPGLU) is a potential amino acid tracer for tumor imaging with high tumor-to-background contrast in several tumor-bearing mice models developed by our research group. Previous studies results have shown that the uptake of 18F-FPGLU in tumor cells is related to the excitatory glutamate transport system XAG-, but its specific molecular transport mechanism is unknown. Experimental study found that the transport mechanism ont only related to excitatory amino acid transporter EAAC1 in lung adenocarcinoma cells, but other transport mechanisms may also involved in it. The expression of other two excitatory amino acid transporters (GLAST and GLT-1) on lung adenocarcinoma tissue were significantly increased than that on normal lung tissues. On this basis, we propose that the GLAST/GLT-1 transporter is the important molecular mechanism of 18F-FPGLU accumulated in tumor cells, and they are important targets for the development of PET imaging agents for glutamate metabolism. This project will establish over-expression and down-regulation of GLAST\GLT-1 on tumor cells and tumor-bearing nude mice models. The correlation between the expression of GLAST\GLT-1 and 18F-FPGLU uptake will be investigated by both cell uptake experiments and PET imaging of 18F-FPGLU on those tumor-bearing models. It provides an important theoretical foundation for the application of 18F-FPGLU in clinical tumor PET imaging and provides new hallmarks for tumor glutamate metabolism PET imaging.