title: Fluorine-18-deoxyglucose positron emission tomography/computed tomography with Ki67 and GLUT-1 immunohistochemistry for evaluation of the radiosensitization effect of oleanolic acid on C6 rat gliomas.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Huiqin
authors.initials: H
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yu
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhao
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000818:Animals; D001692:Biological Transport; D002452:Cell Count; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D064847:Multimodal Imaging; D009132:Muscles / Q000378:metabolism; D009828:Oleanolic Acid / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed
chemical_list: D051272:Glucose Transporter Type 1; D019394:Ki-67 Antigen; D011838:Radiation-Sensitizing Agents; D019788:Fluorodeoxyglucose F18; D009828:Oleanolic Acid