High-resolution Magnetic Resonance Imaging analysis of breast cancer xenograft on the chick chorioallantoic membrane

Abstract

In this thesis an age-adapted cooling regime for immobilization of the chick embryo is proposed. Reliable immobilization completely avoided motion artifacts, enabling high resolution magnetic resonance imaging (MRI) of the chicken embryo and also tumor xenograft on the chorioallantoic membrane (CAM). Tumor growth monitoring was firstly evaluated after xenotransplantation of MDA-MB-231 cells on the CAM. Tumor volumes were monitored from day 4 to day 9 after grafting applying a T2-weighted RARE sequence. Excellent anatomical details could be obtained in the embryo and tumors. Tumor volumes could be quantified over time. At day 9 after grafting, the tumors were collected and compared with the MRI-derived data by histology and weight measurements. Data correlated very well. MR contrast agents (CA) were also assessed for bio-distribution in the CAM model. 80 myl Vasovist was used for assessment at 30 minutes, 3, 5, 20 and 40 hours post-injection in ovo. In tumors the main enhancement was observed in the area surrounding the solid tumor and in the center part, corresponding to the low cell density, which was proved by immune-histology analysis and acknowledged us better about anatomical structures of breast cancer xenograft. To the best of our knowledge, this is the first report on monitoring breast cancer tumor growth by MRI also assess contrast agents bio-distribution in a CAM model in ovo. The results prove the feasibility of high-resolution MRI for longitudinal tumor and organ growth monitoring, and also possess the potential utility for assess novel micelles. The suggested method is promising for future applications such as testing tailored and/or targeted treatment strategies, longitudinal monitoring of tumor development, analysis of therapeutic efficacies of drugs, or assessment of tumor pharmacokinetics. The method provides an alternative to animal experimentation.