Spatial resolutions easily translated to human imaging, but also they allow a closer approximation to tumor masses and metastatic sites found in patients. Increasing recent efforts toward developing tumor models, such as hepatocellular carcinomas, in rats nods to the advantages of using larger animals. In the study of breast cancer, as in other cancers, developing models for metastatic disease is very important, as it remains the principal cause of mortality. A highly metastatic variant of the commonly used hormone-independent MDA-MB-231 human breast adenocarcinoma was developed by Munoz et al. using serial selection for metastasis in the lungs. This mouse xenograft model, known as 231/LM2-4, was shown to establish macroscopic lung nodules only two months after resection of the primary tumor. In the handful of studies on this tumor model to date, mice have been used exclusively to understand breast tumorigenesis and metastasisand to study the efficacy of antivascular agents. Establishment of this pro-metastatic variant in a larger animal model has not been reported. In this study, our aim was to establish the highly metastatic breast Isoacteoside cancer xenograft model 231/LM2-4 in nude rats. Using xenografts to mimic breast cancer in rats is not common, and investigations in rats over the past 50 years have been restricted mainly to chemical carcinogenesis. However, commonly used chemical agents such as 7,12-dimethylbenzanthraceneor N-nitroso-N-methylureainduce mainly hormonedependent adenocarcinomas. Having the ability to also investigate hormone-independent tumors in rats would be beneficial, in light of the histological similarities that have been demonstrated between rat mammary tumors and human breast cancers. In this pilot study, we investigate two different methods for generating xenografts and perform MRI to noninvasively monitor and characterize tumor development in vivo. The use of larger animal models such as the nude rat provides tumor burden that more closely resembles human cancer and is therefore invaluable in the development of advanced non-invasive imaging technologies for clinical application. Image spatial resolutions adequate for sensitive detection and Procyanidin-B2 detailed delineation in a rat can be translated to imaging metastasis in humans, potentially enabling very early cancer detection of both primary and metastatic lesions. However, although immunodeficient strains have been developed from rats, they are not widely used in cancer studies. In this study, we investigated whether or not the LM2 xenograft model, which is a highly metastatic variant of human adenocarcinoma MDA-MB-231, could be successfully established in nude rats. It was shown that the site of implantation dictated the take rate, with 100% success achieved orthotopically when cell injection into the mammary fat pad was guided by ultrasound and zero success subcutaneously in the flank. MRI monitoring of tumor development in vivo demonstrated very rapid progression, with tumors reaching critical size in only 2 to 3 weeks after inoculation. DCE-MRI of Gd contrast kinetics revealed a hypovascular core that increased in size and decreased in contrast uptake as the tumor grew. Histological assessment on H&E and CD34 revealed low vascularity confined mainly to the tumor rim, which is in agreement with DCE-MRI findings. Central necrosis was also observed, which is consistent with hypoxia as a result of rapid growth and exacerbated by the low vascularity of this tumor model.