Objective: The aim of this study was to investigate the radiosensitization effect of oleanolic acid (OA) in an in-vivo C6 rat glioma model using fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) and Ki67 and glucose transporter-1 (GLUT-1) immunohistochemistry(IHC) and evaluate the utility of 18F-FDG PET/CT in assessing early changes after radiotherapy.
Materials and methods: Tumor-bearing rats were divided into four groups: the control group (group A), the OA group(group B), the radiotherapy group (group C), and the OA combined with radiotherapy group (group D). 18F-FDG PET/CT images were obtained to monitor the tumor/muscle (T/M) ratio of 18F-FDG uptake before treatment,1 day after treatment, and 7 days after treatment. Tumor volume changes were also assessed, and hematoxylin and eosin staining and Ki67 and GLUT-1 IHC staining were also carried out.
Results: Before treatment, there were no obvious differences between the T/M ratios (F=0.147, P=0.931)and tumor volumes (F=0.177, P=0.911) among the four groups. At day 1 after treatment, statistical differences were observed in the T/M ratios (F=2.891, P=0.05), with decreased values in groups C and D compared with group A(tCA=2.354, tDA=2.356, P<0.05). At day 7 after treatment,the T/M values of group D were lower than those of the other three groups (tDC=2.416, P=0.03; tDA=8.133,tDB=7.656, P<0.01), and the tumor volumes of group D were significantly decreased compared with group C(t=2.351, P=0.02). There were significant differences in tumor cell densities and in the expression of Ki67 and GLUT-1 in the four groups (F=16.667, 22.082, and 39.555,P<0.001). The T/M ratio showed a significant correlation with the expression of Ki67 and GLUT-1, and our study also found a significant relationship between the expression of Ki67 and the expression of GLUT-1.
Conclusion: OA has a radiosensitization effect on C6 rat glioma tumors in vivo, detected using 18F-FDG PET/CT and Ki67 and GLUT-1 IHC staining. 18F-FDG PET/CT is a potentially sensitive tool for the evaluation of early changes after radiotherapy.