title: Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy.
abstract: BACKGROUND
  Bioluminescent imaging (BLI) is based on the detection of light emitted by living cells expressing a luciferase gene. Stable transfection of luciferase in cancer cells and their inoculation into permissive animals allows the noninvasive monitorization of tumor progression inside internal organs. We have applied this technology for the development of a murine model of colorectal cancer involving the liver, with the aim of improving the pre-clinical evaluation of new anticancer therapies.
  
  
  RESULTS
  A murine colon cancer cell line stably transfected with the luciferase gene (MC38Luc1) retains tumorigenicity in immunocompetent C57BL/6 animals. Intrahepatic inoculation of MC38Luc1 causes progressive liver infiltration that can be monitored by BLI. Compared with ultrasonography (US), BLI is more sensitive, but accurate estimation of tumor mass is impaired in advanced stages. We applied BLI to evaluate the efficacy of an immunogene therapy approach based on the liver-specific expression of the proinflammatory cytokine interleukin-12 (IL-12). Individualized quantification of light emission was able to determine the extent and duration of antitumor responses and to predict long-term disease-free survival.
  
  
  CONCLUSIONS
  We show that BLI is a rapid, convenient and safe technique for the individual monitorization of tumor progression in the liver. Evaluation of experimental treatments with complex mechanisms of action such as immunotherapy is possible using this technology.
authors.affiliation: Division of Gene Therapy and Hepatology, CIMA, University of Navarra, Foundation for Applied Medical Research, Pamplona, Spain. mzabala@stanford.edu
authors.forename: Maider
authors.initials: M
authors.lastname: Zabala
authors.forename: Pilar
authors.initials: P
authors.lastname: Alzuguren
authors.forename: Carolina
authors.initials: C
authors.lastname: Benavides
authors.forename: Julien
authors.initials: J
authors.lastname: Crettaz
authors.forename: Gloria
authors.initials: G
authors.lastname: Gonzalez-Aseguinolaza
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortiz de Solorzano
authors.forename: Manuela
authors.initials: M
authors.lastname: Gonzalez-Aparicio
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Kramer
authors.forename: Jesus
authors.initials: J
authors.lastname: Prieto
authors.forename: Ruben
authors.initials: R
authors.lastname: Hernandez-Alcoceba
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D003952:Diagnostic Imaging / Q000379:methods*; D018450:Disease Progression; D005260:Female; D007150:Immunohistochemistry; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000556:secondary*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D049449:Luminescence; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014463:Ultrasonography
chemical_list: D008156:Luciferases