Quantitative Assessment of Murine Tumors with MicroPET.

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DESCRIPTION (provided by applicant): This proposal seeks to investigate molecular imaging as an efficient tool to assess the progression of precancerous hyperplastic outgrowths and the initiation of tumors in a mouse model of breast cancer. By mimicking the neoplastic progression of breast cancer in humans, mouse models of this type have tremendous potential as a proving ground for preclinical evaluations of the efficacy of new drugs and other novel therapeutics. However, standard histological techniques for assessing are labor intensive and invasive, and therefore limit the use of mouse models for finding new treatments and diagnostic agents in the effort to fight cancer. Small-animal positron emission tomography (microPET) imaging can make a substantial impact in this area by providing in-vivo functional measurements of disease progression, and by following single animals over multiple time points during this period. In order to realize this potential, accurate quantitative descriptions of disease progression and proliferation must be developed and validated. Here, we hypothesize that quantitative methods applied to in-vivo microPET images can be used to efficaciously track the proliferation of precancerous hyperplastic outgrowths as well as the initiation and growth of cancerous tumors in mice. This hypothesis is addressed through three studies. The first proposes collection of microPET data on realistic tumor phantoms embedded in background activity. Since ground truth information about the tumor phantoms will be known, these data will form an ideal dataset for developing and testing the accuracy of quantitation algorithms. The second study proposes a microPET study of longitudinal disease progression in mice along with some tissue harvesting for histological comparisons. The data from this study will allow for a validation of in-vivo microPET quantitation approaches. It will also form a baseline for disease progression against which future datasets can be compared to determine if a therapeutic effect has been achieved. The third study proposes a study in which a well-known therapeutic agent, tamoxifen, is introduced. The data from this study will allow evaluation of the magnitude and statistical significance of a therapeutic effect.