Small Animal Imaging For Monitoring Osteolytic Bone Metastases:
Our laboratory utilizes a well established mouse model of breast cancer metastasis to bone in order to identify molecular targets for the development of better therapeutics. Standard practice has been to monitor bone metastases using standard radiography and bone histomorphometry performed at the end of the experiments. Osteolytic lesions are visible by radiography approximately 14-21 days after tumor cell inoculation via the left cardiac ventricle. However, at this time point, tumors are well established, and there are regions of the skeleton which we are not able to visualize lesions by faxitron analysis. Furthermore, it is not possible to monitor tumor burden in bone in living animals throughout the course of the experiment with current techniques. In order to better understand the relationship between tumor burden and osteolysis, other more sensitive techniques are clearly needed and were utilized in this study. In breast cancer patients, 18[F]-FDG PET scans and 99mTc-MDP–SPECT have been used to track tumor growth, bone metastases and response to therapy.
We hypothesized that 18[F]-FDG MicroPET scans and 99mTc-MDP–MicroSPECT with MicroCT anatomical co-registration would allow us to detect tumors at earlier time points and to detect smaller bone metastases than possible with radiography alone. Here, we present the first use of MicroPET, MicroSPECT, and MicroCT to track tumor burden and bone metastases in a mouse model of breast cancer bone metastases.
Using this model we were able to detect tumor in bone as early as 7 days post tumor cell inoculation using 18[F]-FDG MicroPET, which is much earlier than by radiography. In addition, we are able to detect decreased 99mTC-MDP uptake using MicroSPECT/CT in mice with more severe osteolytic lesions. Furthermore, we were able to detect osteolytic lesions by MicroCT that would otherwise have been undetectable by radiography because of their size and by histological methods because of their site. These techniques will allow us to follow tumor burden and osteolysis through out the course of metastases in the same animals at multiple time points. The ability to do this will greatly enhance our ability to monitor the effect of drug treatments and other interventions on bone metastases.