Breast cancer metastasis to bone is a common debilitating disease. The use of micro-computed tomography (microCT), micro-single-photon emission tomography (microSPECT) and bioluminescent imaging (BLI) techniques are important tools used in research efforts to understand, detect, and ameliorate bone metastasis in animal models. However, it is unclear how repeated x-ray exposure from microCT imaging will affect cancer cell growth and metastasis in vivo. This study sought to determine if weekly x-ray exposure affected breast cancer cell metastasis to bone and also to evaluate the use of BLI and microSPECT for detection of metastatic bone lesions. Female 5 week-old nude mice were randomly assigned to CT exposed (n=15) and non-CT exposed (n=15) treatment groups. Mice received an intracardiac injection of MDA-MB-435 human breast cancer cells transduced with luciferase, or received a sham injection (saline). The CT exposed group of mice received CT irradiation once a week for 5 weeks. All mice underwent weekly BLI to monitor metastasis. After 5 weeks, selected mice (n=6) received Tc-99m-MDP and microSPECT imaging. Pathological evaluation and histomorphometry were used to assess the affect of CT derived x-rays on bone metastasis and determine the sensitivity, specificity, accuracy, and predictive values for BLI. BLI results indicated that there was no significant difference in metastasis between animals that received CT and those that did not (P>0.05); however, histomorphometry of the “knee joints” revealed a significant increase (P=0.029) in tumor area of the hind limb bones in mice that received CT exposure (60%+ 7%) compared to animals that did not receive CT scans (33% + 8%). Compared to histological analysis of bone, BLI to detect metastasis in the leg and spine was determined to have excellent sensitivity (100%), good specificity (80-90%) and accuracy (90-96%), a positive predictive value of 81-93% and a 100% negative predictive value. The specificity and accuracy were less than 100% because the BLI signal thought to be in the bone was actually in other tissue adjacent to bone, and was a limitation of the 2 dimensional BLI method. MicroSPECT imaging could not detect metastatic lesions in the extremities of young nude mice. Thus, multi-modality imaging techniques can be very useful for monitoring bone metastasis, but microCT x-rays should be used judiciously in order to limit irradiation that can stimulate increased metastasis to specific regions of the skeleton.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA