A Novel Method for Quantifying Total Thoracic Tumor Burden in Mice

Abstract

Mouse models are powerful tools to study lung cancer initiation and progression in vivo and have contributed significantly to recent advances in therapy. Using micro-computed tomography to monitor and study parenchymal and extra-parenchymal metastases in existing murine models of lung cancer is challenging owing to a lack of radiographic contrast and difficulty in achieving respiratory gating. To facilitate the analysis of these in vivo imaging studies and study of tumor progression in murine models we developed a novel, rapid, semi-automated method of calculating thoracic tumor burden from computed tomography images. This method, in which commercially available software is used to calculate the mass of the thoracic cavity (MTC), takes into account the aggregate tumor burden in the thoracic cavity. The present study showed that in tumor-free mice, the MTC does not change over time and is not affected by breathing, whereas in tumor-bearing mice, the increase in the MTC is a measure of tumor mass that correlates well with tumor burden measured by lung weight. Tumor burden calculated with our MTC method correlated with that measured by lung weight as well as or better than that calculated using four established methods. To test this method, we assessed metastatic tumor development and response to a pharmacologic PLK1 inhibitor in an orthotopic xenograft mouse model. PLK1 inhibition significantly inhibited tumor growth. Our results demonstrate that the MTC method can be used to study dynamic changes in tumor growth and response to therapeutics in genetically engineered mouse models and orthotopic xenograft mouse models of lung cancer.