Detection of different tumor growth kinetics in single transgenic mice with oncogene-induced mammary carcinomas by flat-panel volume computed tomography

Abstract

Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat-panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene-induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3-dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm(3)) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three-dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP-T mouse, and thereafter show divergent growth rates and distinct vascularization patterns.