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

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 10×105 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. [Copyright &y& Elsevier]