title: Imaging of murine liver tumor using microCT with a hepatocyte-selective contrast agent: accuracy is dependent on adequate contrast enhancement.
abstract: BACKGROUND
  A major limitation in using both spontaneous and implanted murine liver tumor models in cancer research is the inability to accurately detect and monitor tumor volume. Because microCT without contrast enhancement cannot accurately distinguish tumor from normal liver, we sought to determine the accuracy of contrast enhanced microCT for monitoring liver tumors in mice, performed with intravenous (i.v.) injection of ITG, a hepatocyte-selective contrast agent.
  
  
  METHODS
  Twelve female BALB/c mice were injected with 5 x 10(5) CT26 tumor cells in two sites in the liver on day 0, resulting in 24 liver tumors. On days 3, 5, 7, and 10, three mice per day were injected with ITG (0.1 mL ITG/10 g body weight) by tail vein, followed 4 hours later by imaging with microCT (ImTek, Inc.). ITG is transported selectively to hepatocytes by an apoE receptor-mediated process that results in opacification of normal liver parenchyma after i.v. injection. Contrast enhancement on CT scans was graded as good, fair, or poor. After imaging, mice were euthanized to perform gross and histopathologic correlation of liver tumors with CT images.
  
  
  RESULTS
  The mean tumor size on microCT and at histopathologic evaluation was 2.2 and 2.3 mm, respectively (P > 0.05). Regression analysis showed no difference between the CT-measured tumor and the actual tumor size (P > 0.05). The overall accuracy for detection of tumor on microCT was 88%, with one false-positive and two false-negative readings. All three erroneous readings on CT scan occurred in mice in which the contrast enhancement of the liver was poor due to inadequate i.v. injection. Although the overall sensitivity and specificity was 90% and 75%, respectively, this was highly dependent on the degree of contrast enhancement.
  
  
  CONCLUSIONS
  MicroCT with ITG contrast is an excellent means to monitor tumor diameter in murine hepatic tumor models. However, adequate contrast enhancement is critical for accurate imaging.
authors.affiliation: Department of Surgery, University of Wisconsin Medical School, Madison, WI, USA. webers@surgery.wisc.edu
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Weber
authors.forename: Karen A
authors.initials: KA
authors.lastname: Peterson
authors.forename: Benjamin
authors.initials: B
authors.lastname: Durkee
authors.forename: Chen
authors.initials: C
authors.lastname: Qi
authors.forename: Mark
authors.initials: M
authors.lastname: Longino
authors.forename: Thomas
authors.initials: T
authors.lastname: Warner
authors.forename: Fred T
authors.initials: FT
authors.lastname: Lee
authors.forename: Jamey P
authors.initials: JP
authors.lastname: Weichert
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: C486472:1,3-bis(7-(3-amino-2,4,6-triiodophenyl)heptanoyl)-2-oleoylglycerol; D003287:Contrast Media; D014280:Triglycerides