Effects of Glutamine Synthetase on Neovascularization in Glioma: In Vivo MR Vessel Size Imaging and Histology

Title:Effects of Glutamine Synthetase on Neovascularization in Glioma: In Vivo MR Vessel Size Imaging and Histology

Volume: 20

Author(s): Tianwei Song, Dandan Wang, Yanan Zhang, Hong Hao, Guodong Li, Xiping Ding, Zongtao Hu, Zhi Zhang, Yan Liu, Hongzhi Wang, Xianglin Li and Junchao Qian*

Affiliation:

• School of Medical Imaging, Binzhou Medical University, Yantai, 264003, P.R. China
• Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, P.R. China
• Department of Radiation Oncology, School of Medicine, Shandong University, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, P.R. China

Keywords: Glutamine synthetase, Glioma, C6, Microvasculature, Magnetic resonance imaging, Vessel size imaging.

Abstract:

Background: Glutamine Synthetase (GS) could induce vascular sprouting through the improvement of endothelial cell migration in inflammatory diseases. MR vessel-size imaging has been proposed as a valuable approach for visualizing the underlying angiogenic processes in the brain.

Objective: This study aims to investigate the role of GS in the neovascularization of gliomas through the utilization of MR vessel-size imaging and histopathological techniques.

Methods: In this exploratory animal study, we randomly divided the C6 glioma rat models into a control group and an L-methionine sulfoximine (MSO) treatment group. Daily intraperitoneal injections were administered for three consecutive days, starting from day 10 following the implantation of C6 glioma cells in rats. Subsequently, MR vessel size imaging was conducted using a BRUKER 7 T/200 mm MRI scanner, and the MRI results were validated through histopathological examination.

Results: A significant decrease in microvessel density was observed in both the tumor periphery and center areas in the MSO treatment group compared to that in the control group. The mean vessel diameter (mVD) and vessel size index (VSI) did not exhibit significant changes compared to the control group. Moreover, the staining intensity of platelet endothelial cell adhesion molecule-1 (CD31) and GS in the tumor periphery was significantly decreased in the MSO treatment group. Additionally, the MSO treatment demonstrated a substantial inhibition of tumor growth.

Conclusion: GS inhibitors significantly reduced angiogenesis in the periphery area of C6 glioma, exerting an inhibitory effect on tumor progression. Thus, GS inhibitors could be potential therapeutic agents for treating glioma. Additionally, in vivo MR vessel size imaging detects changes in vascularrelated parameters after tumor treatment, making it a promising method for detecting neovascularization in glioma.

Cite this article as:

Song Tianwei, Wang Dandan, Zhang Yanan, Hao Hong, Li Guodong, Ding Xiping, Hu Zongtao, Zhang Zhi, Liu Yan, Wang Hongzhi, Li Xianglin and Qian Junchao*, Effects of Glutamine Synthetase on Neovascularization in Glioma: In Vivo MR Vessel Size Imaging and Histology, Current Medical Imaging 2024; 20 : e15734056287859 . https://dx.doi.org/10.2174/0115734056287859240319062720