A new model of rectal cancer with regional lymph node metastasis allowing in vivo evaluation by imaging biomarkers

Biomed Pharmacother. 2011 Sep;65(6):401-6. doi: 10.1016/j.biopha.2011.04.027. Epub 2011 Jun 12.

Abstract

Object: The work is aimed to develop a murine model of rectal cancer, which could be used to monitor lymph node metastasis development by magnetic resonance imaging (MRI) and optical imaging (OI) techniques.

Subjects and methods: Ht-29 cancer cells were directly injected into the submucosal layer of the rectum of athymic nude mice using trans-anal rectal cancer cell injection (TARCI). Thirty-six mice were inoculated with 10×10(5) cells and five mice were treated with sterile phosphate buffer solution. One to 4 weeks after cell injection, tumor growth was evaluated in vivo using T2-weighted MRI at 4.7T. A further group of animal (n=6) treated with ht-29_luc cells, with the same protocol, was monitored by optical imaging. In both groups, the presence of the primary tumor and of lymph nodes metastasis was confirmed by histology.

Results: In all animals, primary tumors were detectable by MRI, 1 week from TARCI. After 4 weeks primary tumors showed a mean longitudinal diameter of about 2cm. All animals developed regional lymph node metastases. Others organs (e.g. lung or liver) were not affected. In fat-suppressed, T2-weighted MRI, lymph nodes appeared as small areas characterized by hyper-intense signal compared to muscle. OI permitted evaluation of the primary tumor growth in perineal region.

Conclusions: TARCI of ht-29 cells into the rectum of nude mice is a feasible way to obtain a easily reproducible model of regional lymph node metastases could be monitored by magnetic resonance and optical imaging techniques.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Early Detection of Cancer / methods*
  • HT29 Cells
  • Humans
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Luminescent Agents
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / diagnosis*
  • Lymphatic Metastasis / pathology
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Nude
  • Molecular Imaging*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Transplantation / methods
  • Pilot Projects
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Rectal Neoplasms / diagnosis*
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / pathology
  • Rectum / metabolism
  • Rectum / pathology
  • Reproducibility of Results
  • Tumor Burden

Substances

  • Luminescent Agents
  • Neoplasm Proteins
  • Recombinant Proteins
  • Luciferases