The recent technological advancements in MRI, micro-CT and bioluminescence imaging have allowed a concurrent increase in the use of preclinical models of metastasis; models that had traditionally been associated with tedious, expensive and highly variable serial sacrifice methods for efficacy determination. MIR has taken advantage of new imaging innovations by validating reproducibility and treatment response in mouse models of metastasis. Luciferase-expressing cell lines are utilized to determine appearance and site of metastases in bone (Figure 1) and lung. Micro-CT can then be used to provide high spatial resolution of bone osteolytic lesions (Figure 2) and lung tumor nodules (Figure 3). Figure 1shows treatment response in a PC3 model of bone metastasis. T2-weighted MRI can be used to quantify liver metastases due to the high natural contrast between high iron-containing normal liver tissue and tumor tissue. These models rely on intracardiac, intravenous, or intrasplenic injection of tumor cells. MIR is currently validating breast, pancreas and prostate orthotopic models that spontaneously metastasize, enabling testing of early stage, metastasis prevention therapies.

Figure 2:

Micro-CT images acquired using the GE RS150 scanner at MIR. The images show knee osteolytic bone damage in a PC3 model of bone metastasis. The left image is the knee of an untreated control mouse and the right image shows the knee of a mouse treated with rapamycin (Q3Dx2,3)x4wk.

Figure 3:

Lung metastasis imaging at MIR. The figure shows a segmented image showing metastases (red) in normal lung (green) in a B16 intravenous model of lung metastasis.

Bioluminescence imaging is able to detect and follow PC3 metastases in vivo. Metastases identified by bioluminescence imaging can be characterized as bone lesions by micro-CT in vivo. Progression of bone involvement can be followed by serial micro-CT. Bone metastases can be further visualized by 3D volume rendering of the CT data set.