Abstract 3983: Real-time imaging of human thyroid cancer progression in a fluorescent orthotopic nude mouse model

Abstract

Abstract We report here a novel orthotopic mouse model of human thyroid cancer that can be imaged non-invasively with the use of red fluorescent protein (RFP). Human thyroid cancer cell lines NPA (papillary) and KAK-1 (anaplastic) were stably transfected to express RFP or the green fluorescent protein (GFP). The cells were then injected into the thyroid glands of 8-week old athymic mice. The animals were noninvasively imaged weekly, and sacrificed when premorbid. Their tumor was subsequently resected en bloc with the respiratory system for further processing and analysis. H&E staining was performed to confirm the pathological diagnosis. Both anaplastic and papillary thyroid cancer cell lines led to the robust development of orthotopic fluorescent tumors in nude mice. While RFP-expressing tumors were easily identified transcutaneously, autofluorescence of the skin prevented visualization of GFP-expressing tumors, making GFP a suboptimal model. Injection of 5 × 10^5 cells was as efficacious in allowing tumor development as 5 × 10^6 cells. Tumors were first visualized for both cell lines via whole-body noninvasive imaging as early as four weeks post-implantation and could be monitored over time. The time to premorbid conditions varied greatly between mice and seemed to be associated with the tumor growth pattern rather than tumor size. The earliest appearance of morbidity was five weeks post-implantation in an animal with cachexia due to local compression of the esophagus by the tumor. Other mice died at later stages from metastatic disease. The bright fluorescence of the tumors allowed identification of multiple micrometastases at necropsy in the lungs, lymph nodes, and the vascular system, lesions that were not visible under white light. In summary, we have developed a novel orthotopic fluorescent mouse model of thyroid cancer that should serve a valuable role in the understanding of this disease and in the evaluation of new therapeutics, allowing assessment of the tumor response over time. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3983.