(18)F-FDG PET has been widely used in the management of malignant tumors. Lactate dehydrogenase A (LDHA) plays an important role in the development, invasion, and metastasis of malignancies. However, the relationship between (18)F-FDG accumulation and LDHA expression has not been investigated.
Methods: Retrospective analysis was conducted for 51 patients with lung adenocarcinomas who underwent (18)F-FDG PET. The relationship between maximum standardized uptake value and the expression of LDHA, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) were examined. RNA interference was used to analyze the role of LDHA in tumor metabolism and growth in A549 cells. The AKT, also known as protein kinase B, pathway was also investigated to evaluate the molecular mechanisms of the relationship between LDHA expression and (18)F-FDG uptake.
Results: Maximum standardized uptake value was significantly higher in the LDHA high-expression group than the LDHA low-expression group (P = 0.018). GLUT1 expression in lung adenocarcinomas was positively correlated with (18)F-FDG accumulation and LDHA expression whereas HK2 expression was not. Knockdown of LDHA led to a significant decrease in GLUT1 expression, (18)F-FDG uptake, and cell proliferation. The activated form of AKT was also decreased after LDHA knockdown.
Conclusion: LDHA increases (18)F-FDG accumulation into non-small cell lung cancer, possibly by upregulation of GLUT1 expression but not HK2 expression. LDHA may modulate (18)F-FDG uptake in lung adenocarcinomas via the AKT-GLUT1 pathway. These results indicate that (18)F-FDG PET/CT may predict LDHA expression levels and response to anti-LDHA therapy in lung adenocarcinomas.
Keywords: 18F-FDG uptake; GLUT1; LDHA; glycolysis; lung adenocarcinomas.
© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.