Abstract
Imaging the mouse has become a valuable adjunct to genomic and cancer research. Although tomographic techniques such as high-resolution positron emission tomography (microPET) and computed tomography (microCT) are extremely useful, there is also a need for the rapid assessment of mouse anatomy and function at very low radiation doses, with low cost and high throughput. A system was designed using a stimulable phosphor BaFBr imaging plate (commonly called computed radiography [CR]) as the detector. A planar emission image (I-125) is acquired onto one side of the 18 cm × 24 cm CR detector. Subsequent to the emission image acquisition, precise translation of the mouse platform over the CR plate allows the acquisition of an X-ray radiographic image onto the other side of the same CR plate. The image is then read out in a CR reader, which produces a 1770 × 2370 pixel digital image with 0.100 mm pixel pitch. The I-125 and X-ray images are extracted from the larger image, and are mechanically registered, allowing the functional I-125 emission data to be overlaid onto the anatomical X-ray image. Because the CR imaging plates and other required hardware are relatively inexpensive, it is possible that up to 20 mice could be imaged simultaneously using 20 imaging plates, limited only by how many mice can be safely anesthetized and monitored by the technician(s). Once the mice are safely back in their cages, the CR plates can then be read out and the images processed. The overall design of the dual imaging system will be discussed, and the results of a prototype system currently in our laboratory will be presented. Monte Carlo techniques were used to assess the X-ray-associated radiation dose levels with the hybrid imaging system, and the findings suggest that the radiation levels due to the X-ray procedure are far lower than for microCT. We conclude that for appropriate research applications such as monitoring tumor growth over time, or monitoring tumor regression due to therapy, the hybrid imaging system may provide useful tumor kinetic information with high spatial and temporal resolution, and using low radiation dose levels.
Highlights
The remarkable generation of scores of increasingly sophisticated mouse models of mammary cancer over the past two decades has provided tremendous insights into molecular derangements that can lead to cancer
We report that somatic mutations of p53 in mouse mammary epithelial cells lead to ERα-positive and ERαnegative tumors. p53 inactivation in pre-pubertal/pubertal mice, but not in adult mice, leads to the development of ERα-positive tumors, suggesting that developmental stages influence the availability of ERα-positive tumor origin cells
Genetic alterations commonly observed in human breast cancer including c-myc amplification and Her2/Neu/erbB2 activation were seen in these mouse tumors
Summary
Transgenic Oncogenesis Group, Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA. The remarkable generation of scores of increasingly sophisticated mouse models of mammary cancer over the past two decades has provided tremendous insights into molecular derangements that can lead to cancer. The relationships of these models to human breast cancer, remain problematic. P53 inactivation in pre-pubertal/pubertal mice, but not in adult mice, leads to the development of ERα-positive tumors, suggesting that developmental stages influence the availability of ERα-positive tumor origin cells. These tumors have a high rate of metastasis that is independent of tumor latency. Since it is feasible to isolate ERα-positive epithelial cells from normal mammary glands and tumors, molecular mechanisms underlying ERα-positive and ERα-negative mammary carcinogenesis can be systematically addressed using this model
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