title: Dynamic contrast-enhanced (DCE) MRI assessment of microvascular characteristics in the murine orthotopic pancreatic cancer model.
abstract: OBJECTIVE
  The aim of this study was to assess the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters between two contrast agents in a murine orthotopic pancreatic cancer model and to evaluate the tumor heterogeneity and the potential association between kinetic parameters and angiogenic markers such as the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression by immunohistochemistry.
  
  
  METHODS
  Human pancreatic adenocarcinoma cell line MIAPaCa-2 was injected into the pancreas of BALB/C nu/nu mice. DCE-MRI was performed using Gd-DTPA and Gd-EOB-DTPA. Quantitative and semi-quantitative vascular parameters (K(trans), Kep, Ve and AUC) were calculated by using a dedicated postprocessing software program. Values were compared with tumor rim, tumor core and the entire tumor. The MVD and VEGF expressions between tumor rim and tumor core were also compared.
  
  
  RESULTS
  There were no significant differences in K(trans), Kep, Ve, and AUC values of the three groups when using Gd-DTPA. However there were significant differences in K(trans), Kep, and AUC values of the three groups when using Gd-EOB-DTPA (P=0.014, 0.022, 0.007, respectively), in addition, the K(trans) and Kep values of tumor core were significantly lower than those of the entire tumor (adjusted P=0.014 and 0.027, respectively), the AUC values of core were significantly lower than those of the entire tumor and rim (adjusted P=0.039 and 0.009, respectively). Immunohistology results revealed that MVD and VEGF expression in the tumor rim was significantly higher than that in the core. There was positive correlation between AUC and MVD, VEGF.
  
  
  CONCLUSIONS
  The murine orthotopic pancreatic cancer model provides an ideal animal model to study human pancreatic cancer. It can more sensitively semi-quantitatively and quantitatively analyze tumor angiogenesis through selecting the albumin-binding contrast agent.
authors.affiliation: Department of Intervetional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Radiology, Shanghai jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Lv
authors.affiliation: Department of Protistology, Guangdong Jiaying Medical College, Meizhou, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Siemens Shenzhen Magnetic Resonance Ltd, Siemens MRI Center, Shenzhen, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiuzhong
authors.initials: X
authors.lastname: Yao
authors.affiliation: Cancer Research Institute, Shanghai Cancer Center, Fudan University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: zeng.mengsu@zs-hospital.sh.cn.
authors.forename: Mengsu
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Cancer Research Institute, Shanghai Cancer Center, Fudan University, Shanghai, China. Electronic address: liyingyi@fudan.edu.cn.
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Intervetional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: xlwang-shmu@vip.sina.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000648:ultrastructure*; D009389:Neovascularization, Pathologic; D010179:Pancreas / Q000098:blood supply / Q000473:pathology / Q000648:ultrastructure; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000473:pathology* / Q000648:ultrastructure; D042461:Vascular Endothelial Growth Factor A / Q000648:ultrastructure
chemical_list: D003287:Contrast Media; D042461:Vascular Endothelial Growth Factor A; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA
keywords: DCE-MRI; Gd-DTPA; Gd-EOB-DTPA; Pancreatic cancer