title: [Gene-targeted radiation therapy mediated by radiation-sensitive promoter in lung adenocarcinoma and the feasibility of micro-PET/CT in evaluation of therapeutic effectiveness in small animals].
abstract: OBJECTIVE
  To explore the combined anti-tumor effect of radiation therapy and gene-targeted suppression of tumor neovasculature in lung adenocarcinoma in vivo, and to explore the feasibility of micro-PET/CT in dynamic evaluation of treatment effectiveness.
  
  
  METHODS
  Thirty 5-6-week old male BALB/c nude mice were used in this study. The mouse models of xenotransplanted human lung adenocarcinoma were divided into 5 groups at random, six mice in each group: the control group, radiation treatment alone group and three groups of recombinant baculovirus plus radiation treatment (intratumoral injection, tail vein injection, and intramuscular injection). The tumor volume was measured every 2 days. Growth delay time (GD) and growth inhibition rate was calculated. FDG metabolism was evaluated by micro-PET-CT before and after treatment. The expressions of VEGF, CD31 and Ki-67 were detected by immunohistochemistry (IHC).
  
  
  RESULTS
  The tumor growth delay was >12 days, and the tumor inhibition rate was >45% in the recombinant baculovirus combined with radiotherapy groups, significantly higher than that of the radiotherapy alone group (P < 0.05). Immunohistochemical analysis showed that the expressions of VEGF, CD31 and Ki-67 were significantly lower than that in other groups (P < 0.05). The micro-PET-CT assessment showed that the FDG-metabolism in the recombinant baculovirus combined with radiotherapy groups was significantly reduced (P < 0.05), and the SUVmax (FDG metabolism) of transplanted tumors after treatment was also markedly decreased in comparison with that of the control group. The tumor volume after treatment was significantly correlated with SUVmax in the recombinant baculovirus intratumoral injection + radiotherapy group(r = 0.976), recombinant baculovirus intravenous injection + radiotherapy group (r = 0.954), recombinant baculovirus intramuscular injection + radiotherapy group (r = 0.929), and radiotherapy alone group (r = 0.871, P < 0.05).
  
  
  CONCLUSIONS
  The recombinant baculovirus containing Egr1 promoter and K5 gene combined with radiotherapy enhances the suppressing effect on the growth of lung adenocarcinoma in the tumor-bearing nude mice. The inducibility of Egr1 promoter by radiation allows the targeting and controllability of treatment. Micro-PET-CT results have a good correlation with the treatment effectiveness. Therefore, it can be used in real-time evaluation of tumor metabolic function in vivo.
authors.affiliation: Department of Oncology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Haoping
authors.initials: H
authors.lastname: Xu
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Yening
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Email: lb10363@rjh.com.cn.
authors.forename: Biao
authors.initials: B
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000502:physiology; D019788:Fluorodeoxyglucose F18; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000235:genetics* / Q000502:physiology; D010958:Plasminogen / Q000235:genetics* / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic; D011897:Random Allocation; D011994:Recombinant Proteins / Q000235:genetics; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D019394:Ki-67 Antigen; D010446:Peptide Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C491499:plasminogen kringle 5; D019788:Fluorodeoxyglucose F18; D010958:Plasminogen