3796

In vivo imaging of a mouse model of PC-3 bone metastasis

Tuesday, Apr 19, 2005, 8:00 AM -12:00 PM

Board #11

Jonathan B. Moody, Richard Lister, Patrick McConville, Alnawaz Rehemtulla, William L. Elliott, Wilbur R. Leopold. MIR Preclinical Services, Ann Arbor, MI, University of Michigan, Ann Arbor, MI

Introduction: In vivo imaging of small animal models in oncology is an increasingly important tool in preclinical drug development. This is particularly true for those models that have traditionally required serial sacrifice, such as models of lung and bone metastasis. Using a murine model of bone metastasis based on a PC-3 cell-line, we have utilized whole-body x-ray micro-computed tomography (μCT) to identify bone lesions and have serially imaged individual animals over time to monitor the spread and growth of bone metastases.
Methods: PC-3 cells were used to inoculate 40 SCID mice using an intra-cardiac (ICr) injection. Cells were prepared using a small amount of blue food dye to verify the ICr injection. After 14 days, the development of bone lesions was evaluated using μCT at 100 μm isotropic resolution. Once lesions were identified in the long bones, μCT was used to quantitatively follow progression of disease. Organs and bones of selected animals were harvested at necropsy for visual and histological evaluation.
Results and Discussion: ICr injection of PC-3 cells was successful in 80% of animals as determined by dye distribution. Lesions were found by μCT in the mandible and hind limbs, and additional metastases were found at necropsy in the heart and lungs. Figure 1 shows an example of a left proximal tibial lesion approximately 3-3.5 mm in diameter. The PC-3 origin of bone lesions and lesion size in the μCT data correlated well with the histological evaluation.
Conclusion: Bone lesions were detected and followed over time by high-resolution μCT in a robust mouse model of PC-3 bone metastasis. This model could be extended to other cell-lines and will potentially allow the non-invasive, quantitative evaluation of metastatic tumor response to chemotherapeutics.
Figure 1: Bone lesion shown on left proximal tibia (white arrow).