Tumor imaging technologies in mouse models

Abstract

In this chapter, we describe protocols for tumor imaging technologies in mouse models. These models utilize human cancer cell lines which have been genetically engineered to selectively express high levels of green fluorescent protein (GFP) or red fluorescent protein (RFP). Tumors with fluorescent genetic reporters are established subcutaneously in nude mice, and fragments of the subcutaneous tumors are then surgically transplanted onto the orthotopic organ. Locoregional tumor growth and distant metastasis of these orthotopic implants occur spontaneously and rapidly throughout the abdomen in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time quantitative fluorescence imaging of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. Transplantation of RFP-expressing tumor fragments onto the pancreas of GFP- or cyan fluorescent protein (CFP)-expressing transgenic nude mice was used to facilitate visualization of tumor-host interaction between the pancreatic cancer cells and host-derived stroma and vasculature. Such in vivo models have enabled us to visualize in real time and acquire images of the progression of pancreatic cancer in the live animal, and to demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on a variety of malignancies. We discuss studies from our laboratory that demonstrate that fluorescence imaging in mice is complementary to other modalities such as magnetic resonance imaging (MRI) or ultrasound. These fluorescent models are powerful and reliable tools with which to investigate metastatic human cancer and novel therapeutic strategies directed against it.