Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy.
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.
Zabala
Maider
M
Division of Gene Therapy and Hepatology, CIMA, University of Navarra, Foundation for Applied Medical Research, Pamplona, Spain. mzabala@stanford.edu
Alzuguren
Pilar
P
Benavides
Carolina
C
Crettaz
Julien
J
Gonzalez-Aseguinolaza
Gloria
G
Ortiz de Solorzano
Carlos
C
Gonzalez-Aparicio
Manuela
M
Kramer
Maria Gabriela
MG
Prieto
Jesus
J
Hernandez-Alcoceba
Ruben
R
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
D008156:Luciferases