PET imaging of development and malignant transformation in a mouse model of mammary intraepithelial neoplasia

The purpose of this work is to explore image quantitation in small-animal positron emission tomography (PET) as a tool for following proliferation and malignant transformation of mammary intraepithelial neoplasia outgrowths in vivo in laboratory mice. The expected application of the work is preclinical evaluations of breast cancer therapeutics. For nonpalpable or prepalpable disease, current practice involves large cohorts of mice with groups sacrificed at each time point. Because of the substantial variability in tumor development, numerous mice are needed at each time point to obtain statistical power. In vivo imaging techniques have the ability to follow a single mouse over multiple time points in longitudinal studies, and therefore reduce the number of mice needed for evaluation. Longitudinal studies offer an additional increase in statistical power by being able to control for the condition of disease (e.g. tumor size) at onset of treatment. Critical to the success of this approach is the ability to extract meaningful quantitative markers of disease. The study reported here describes a computational approach to extracting quantitative markers of disease progression and proliferation in longitudinal PET studies, and an analysis of the increase in statistical power due to temporal correlations in the extracted markers.