title: Detection of pancreatic ductal adenocarcinoma in mice by ultrasound imaging of thymocyte differentiation antigen 1.
abstract: OBJECTIVE
  Early detection of pancreatic ductal adenocarcinoma (PDAC) allows for surgical resection and increases patient survival times. Imaging agents that bind and amplify the signal of neovascular proteins in neoplasms can be detected by ultrasound, enabling accurate detection of small lesions. We searched for new markers of neovasculature in PDAC and assessed their potential for tumor detection by ultrasound molecular imaging.
  
  
  METHODS
  Thymocyte differentiation antigen 1 (Thy1) was identified as a specific biomarker of PDAC neovasculature by proteomic analysis. Up-regulation in PDAC was validated by immunohistochemical analysis of pancreatic tissue samples from 28 healthy individuals, 15 with primary chronic pancreatitis tissues, and 196 with PDAC. Binding of Thy1-targeted contrast microbubbles was assessed in cultured cells, in mice with orthotopic PDAC xenograft tumors expressing human Thy1 on the neovasculature, and on the neovasculature of a genetic mouse model of PDAC.
  
  
  RESULTS
  Based on immunohistochemical analyses, levels of Thy1 were significantly higher in the vascular of human PDAC than chronic pancreatitis (P = .007) or normal tissue samples (P < .0001). In mice, ultrasound imaging accurately detected human Thy1-positive PDAC xenografts, as well as PDACs that express endogenous Thy1 in genetic mouse models of PDAC.
  
  
  CONCLUSIONS
  We have identified and validated Thy1 as a marker of PDAC that can be detected by ultrasound molecular imaging in mice. The development of a specific imaging agent and identification of Thy1 as a new biomarker could aid in the diagnosis of this cancer and management of patients.
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
authors.forename: Kira
authors.initials: K
authors.lastname: Foygel
authors.forename: Huaijun
authors.initials: H
authors.lastname: Wang
authors.forename: Steven
authors.initials: S
authors.lastname: Machtaler
authors.forename: Amelie M
authors.initials: AM
authors.lastname: Lutz
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.forename: Marybeth
authors.initials: M
authors.lastname: Pysz
authors.forename: Anson W
authors.initials: AW
authors.lastname: Lowe
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.forename: Tricia
authors.initials: T
authors.lastname: Carrigan
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Brentnall
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Willmann
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000000981:diagnostic imaging; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000175:diagnosis* / Q000000981:diagnostic imaging; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000000981:diagnostic imaging; D018800:Thy-1 Antigens / Q000032:analysis*; D014183:Transplantation, Heterologous; D014463:Ultrasonography
chemical_list: D014408:Biomarkers, Tumor; D018800:Thy-1 Antigens
keywords: CD90; Diagnostic Test; IHC; MB; Molecular Imaging; PDAC; Pancreatic Cancer; Thy1; WT; immunohistochemistry; microbubble; pancreatic ductal adenocarcinoma; thymocyte differentiation antigen 1; wild-type