中文摘要
谷氨酰胺(Gln)代谢是肿瘤分子影像学研究的热点。正电子核素标记的Gln (18F-Gln)有望成为另一个重要的肿瘤显像剂,然而许多肿瘤细胞除了从血液中摄取Gln外,还可以在细胞内Gln合成酶(GS)的作用下合成Gln。Gln的内源合成很可能会影响肿瘤细胞对外源性Gln的摄取,进而使18F-Gln的显像结果低估肿瘤细胞的实际Gln代谢水平。.本研究通过细胞实验,观察GS酶表达水平变化时,细胞对Gln的摄取、Gln运转蛋白的表达、Gln摄取量和细胞内谷氨酰胺酶(GLS)之间的对应关系变化情况。通过荷瘤鼠实验,研究GS酶表达水平不同的肿瘤组织中,18F-Gln显像结果和GLS表达水平之间的关系、13N-NH3显像结果和GS酶表达水平之间的关系、GLS表达水平和这两种显像剂的显像结果之间的关系。以阐明GS酶的表达对18F-Gln显像结果的影响,并探索用两种显像剂来反映肿瘤组织的真实Gln代谢水平
英文摘要
Tumorous glutamine metabolism is a very hot topic in the field of molecuar imaging. Glutamine has been radio-labelled with positron nuclide 18F successfully recently and has the potential to be another important tracer for tumor imaging. However, in addition to uptaking glutamine from plamza, many tumor cells could synthesize glutamine themselves with glutamine synthetase (GS) as catalyzator. This endougeneous glutamine synthesis might decrease the uptake of glutamine form plazma, making the 18F-glutamine imaging result underestimates the glutamine metabolic level. In a preliminary experiment with breast cancer cells, we found that the consumption of glutamine in culture media increased significantly after the inhibition of GS expression. .In this study, we are going to regulate the expression of GS in tumor cells, and then observe the consumption of glutamine in culture media, the expression of glutamine transportor on cellular surface, and the relationship between glutamine uptake rate and the expression of glutaminase (GLS). In animal experiments with nude mice, we are going to investigate the relatioships between 13N-NH3 uptake rate and the expression of GS, between 18F-glutamine uptake rate and GLS expression, and between GLS expression and the uptake results of 13N-NH3 and 18F-glutamine. Finally, we aim to illustrate the effection of GS expression on 18F-glutamine imaging, and express the glutamine metabolic level with imaging results of 13N-NH3 and 18F-glutamine.
