INTRODUCTION: Mouse models of metastasis commonly require serial sacrifice for evaluation of therapeutic response. MRI has the potential to non-invasively quantify metastatic tumor burden over time, however, validation of MRI methodology in metastatic mouse models is lacking. We sought to evaluate 7T MRI in a colorectal liver metastasis model. METHODS: Liver metastases were established in BALB/C mice by intra-splenic injection of a C26 single cell suspension. A metastatic cell line was derived by serial passage, then harvest/re-injection of cells from liver metastases, over multiple iterations. Both T2-weighted (T2w) and gadolinium- and iron-oxide-contrast-enhanced MRI were compared for delineating metastases during their development, both ex vivo and in vivo. RESULTS AND DISCUSSION: A metastatic cell line was derived, with 80% of injected mice developing metastases within one week. Ex vivo MRI demonstrated that metastases as small as 0.5 mm in diameter could be delineated from normal liver without the use of contrast agents. In the living animal, metastases as small as 2 mm in diameter could be reproducibly delineated using T2w scans. Intravenous injection of both Magnevist (gadolinium contrast agent) and Feridex (iron oxide contrast agent) increased the contrast between normal liver and metastatic tissue, facilitating identification of small metastases. CONCLUSION: A robust model of metastatic liver disease was developed using intrasplenic injection without surgery. Metastases in the liver were delineated by T2w anatomical MRI. However, in the living animal, delineation of metastases < 2 mm in diameter, using T2w anatomical MRI was difficult due to lower resolution in the larger field of view, and sensitivity loss due to breathing motion. Intravenous use of both gadolinium- and iron oxide-containing contrast agents enhanced the delineation of these small metastases. Future work will involve the use of standard chemotherapeutic agents in the model, and development of a C26 subcutaneous implant model for liver metastasis.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]