title: Detection of precursor lesions of pancreatic adenocarcinoma in PET-CT in a genetically engineered mouse model of pancreatic cancer.
abstract: BACKGROUND
  Pancreatic cancer is among the most dismal of human malignancies. The 5-year survival rate is lower than 5%. The identification of precursor lesions would be the main step to improve this fatal outcome. One precursor lesions are called pancreatic intraepithelial neoplasia (PanIN) and are graduated in grade 1 to 3, whereas grade 3 is classified as carcinoma in situ. Currently, no reliable, noninvasive imaging technique (e.g., ultrasound, computed tomography, magnet resonance imaging) exists to verify PanINs.
  
  
  METHODS
  Recently, a transgenic mouse model of pancreatic cancer was established in which the tumor progression of human pancreatic carcinoma is reproduced. These so-called Pdx-1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+mice develop PanINs, which transform to invasive growing pancreatic carcinoma. The pancreata of mice of different ages were immunohistochemically stained using α-GLUT-2 antibodies. Furthermore, mice underwent positron emission tomography (PET)-computed tomography (CT) with (18)F-fluorodeoxyglucose (FDG) to evaluate early detection of PanIN lesions.
  
  
  RESULTS
  An expression of GLUT-2 in murine PanINs was found in PanINs of grade 1B and higher. This finding is associated with an elevated glucose metabolism, leading to the detection of precursor lesions of pancreatic cancer in the FDG PET-CT scan. In addition, immunohistochemical staining of GLUT-2 was detectable in 45 (75%) of 60 human PanINs, whereas PanINs of grade 1B and higher showed a very extensive expression.
  
  
  CONCLUSIONS
  In conclusion, we demonstrate for the first time that an elevated glucose metabolism occurs already in precursor lesions of murine and human pancreatic carcinoma. These findings are the basis for the detection of precursor lesions by PET-CT, thereby helping improving the prognosis of this devastating disease.
authors.affiliation: Department of Surgery, Philipps University Marburg, Marburg, Germany. fendrich@med.uni-marburg.de
authors.forename: Volker
authors.initials: V
authors.lastname: Fendrich
authors.forename: Ralph
authors.initials: R
authors.lastname: Schneider
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Ilse D
authors.initials: ID
authors.lastname: Jacobsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Opfermann
authors.forename: Detlef K
authors.initials: DK
authors.lastname: Bartsch
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002278:Carcinoma in Situ / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D019788:Fluorodeoxyglucose F18 / Q000032:analysis / Q000378:metabolism; D005818:Genetic Engineering; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000032:analysis; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011230:Precancerous Conditions / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology
chemical_list: D051273:Glucose Transporter Type 2; D019788:Fluorodeoxyglucose F18; D005947:Glucose