Abstract LB-329: Multiple-resolution characterization of tumor heterogeneity as associated with disease progression in a mouse model of colorectal cancer

Abstract

Abstract The ability to engineer models to express endogenous fluorophores has become an invaluable tool for studying tumor biology. The utility of these models is limited by the sensitivity and resolution of currently available imaging platforms. In vivo techniques enable longitudinal studies in which changes in fluorescent markers, tumors, and whole organs can be monitored over time. In vivo fluorescence suffers from poor sensitivity and resolution owing to the high absorption and scatter of light in biological tissue. While ex vivo fluorescence techniques allow for high resolution evaluation and characterization, these techniques typically only focus on a small samples of tissue instead of whole animals. Using a Cryo-Fluorescence Tomography (CFT) imaging approach, an imaging modality based on serial slicing and off-the-block fluorescence imaging, we can bridge the gap between in vivo and ex vivo resolution of the entire animal. As proof of concept, a novel mouse model expressing fluorophores was evaluated and characterized. Individual cells were labeled with either EGFP or tdTomato prior to tumor initiation. Intestinal tumors were induced through loss of Apc, the activation of PI3K, or both. Tumor heterogeneity and grade were assessed by traditional histopathology, individual-tissue CFT, and whole-animal CFT. Using CFT, serial sectioning and 3D-reconstruction of whole tissues were achieved at 10-50 µm resolution.The multi-resolution imaging approach of this model enabled visualization of molecular and histopathological information from a common in vivo resolution (1mm) to whole-tissue resolution. The CFT platform enabled a 3D data set at a resolution that was not previously available in traditional histopathology. CFT as a molecular tissue imaging technique has proven its utility as a complimentary assay in preclinical oncology studies allowing several characteristics of tumors including heterogeneity, growth, and malignant spread to be readily assessed. Citation Format: Mohammed Farhoud, Alyssa Leystra, Dawn M. Albrecht, Mathew Brevard, Hemi Dimant, Robert Holt, Richard B. Halberg. Multiple-resolution characterization of tumor heterogeneity as associated with disease progression in a mouse model of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-329.