使用对比增强MRI研究原位胶质瘤SRG大鼠模型中血脑屏障渗漏的进展

Gliomas are the most common type of primary brain tumors. Innovative therapies are vital to improve treatment outcomes but to be efficient, trafficking across the blood brain barrier (BBB) is required. For this advent, animal models provide important information prior to clinical studies. Among the different in vivo models, orthotopic models mimic the biological environment. In addition to traditional mouse models, novel immunocompromised rat models offer new approach to preclinical efficacy testing facilitating PK/PD studies for IND enabling studies. SRG rats enable high engraftment rates and rapid growth of a variety of human tissues and tumors. Severe immunodeficiency ensures high engraftment rates and larger organism size allows larger sample collection e.g. for blood biomarker analysis. Especially in the brain tumor research, imaging has a central role in clinical diagnosis and as a prognostic factor to monitor therapy response. It enables longitudinal monitoring in a fully translational manner. Magnetic resonance imaging (MRI) offers unprecedented soft tissue contrast, high spatial resolution and non-invasive nature renders MRI in rodents a perfect tool for preclinical work in oncological applications. In addition to monitor tumor growth, cerebral blood flow (CBF) and leakage of BBB can be measured with a contrast agent. Perfusion indicates angiogenesis in tumor, one hallmark of most malignant gliomas as well the leakage status of glioma is critical to understand for possible therapeutic intervention. The purpose of this work was to establish orthotopic glioma model in SRG rats using U87MG cells. Development of brain pathologies were longitudinally monitored in vivo using MRI. Key readouts were anatomical visualization of abnormalities, tumor volumetry, vascularization in tumor, CBF and development of BBB leakage. Differences in CBF represents mass effect from brain tumors impairing blood flow in the surrounding brain parenchyma. As a conclusion, translational in vivo imaging techniques were applied to study orthotopic tumor progression. These readouts provide a powerful and translational research tool together with oncological disease animal models with detailed understanding about disease progression and improved treatment intervention design.