Multimodal Optical, X-Ray CT, and SPECT Imaging of a Mouse Model of Breast Cancer Lung Metastasis
2013
Tumor heterogeneity is recognized as a major issue within clinical oncology, and the concept of
personalized molecular medicine is emerging as a means to mitigate this problem. Given the vast number of
cancer types and subtypes, robust pre-clinical models of cancer must be studied to interrogate the molecular
mechanisms involved in each scenario. In particular, mouse models of tumor metastasis are of critical
importance for pre-clinical cancer research at the cancer cell molecular level. In many of these experimental
systems, tumor cells are injected intravenously, and the distribution and proliferation of these cells are
subsequently analyzed via ex vivo methods. These techniques require large numbers of animals coupled with
time-consuming histological preparation and analysis. Herein, we demonstrate the use of two facile and noninvasive
imaging techniques to enhance the study of a pre-clinical model of breast cancer metastasis in the
lung. Breast cancer cells were labeled with a near-infrared fluorophore that enables their visualization. Upon
injection into a living mouse, the distribution of the cells in the body was detected and measured using whole
animal fluorescence imaging. X-ray computed tomography (CT) was subsequently used to provide a
quantitative measure of longitudinal tumor cell accumulation in the lungs over six weeks. A nuclear probe for
lung perfusion, 99mTc-MAA, was also imaged and tested during the time course using single photon emission
computed tomography (SPECT). Our results demonstrate that optical fluorescence methods are useful to
visualize cancer cell distribution patterns that occur immediately after injection. Longitudinal imaging with X-ray
CT provides a convenient and quantitative avenue to measure tumor growth within the lung space over several
weeks. Results with nuclear imaging did not show a correlation between lung perfusion (SPECT) and
segmented lung volume (CT). Nevertheless, the combination of animal models and noninvasive optical and CT
imaging methods provides better research tools to study cancer cell differences at the molecular level.
Ultimately, the knowledge gleaned from these improved studies will aid researchers in uncovering the
mechanisms mediating breast cancer metastasis, and eventually improve the treatments of patients in the
clinic.
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