IN VIVO MR PERMEABILITY IN MOUSE XENOGRAFT MODEL OF GLIOBLASTOMA MULTIFORMA

多形性胶质母细胞瘤小鼠异种移植模型的体内 MR 通透性

• 批准号: 7601205
• 负责人: Gerald Arthur Grant
• 金额: $ 1万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601205
• 关键词: Aminoisobutyric Acids; Anesthesia procedures; Blood; Blood Vessels; Brain; Brain Neoplasms; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Data; Drug Delivery Systems; Funding; Glioblastoma; Goals; Grant; Heterogeneity; Human; Image; Injection of therapeutic agent; Institution; Intracranial Neoplasms; Label; Magnetic Resonance Imaging; Measurement; Modeling; Molecular; Mus; Nude Mice; Permeability; Pilot Projects; Prohance; Rate; Research; Research Personnel; Resources; Source; Standards of Weights and Measures; Tail; United States National Institutes of Health; Veins; Xenograft Model; Xenograft procedure; day; in vivo; mouse model; size; tumor; tumor growth; tumor xenograft

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this study is to perform in vivo MR permeability studies to assess the correlation of BBB permeability with tumor size and rate of tumor growth in a mouse xenograft brain tumor model. Congenitally athymic nude mice will be injected with an intracranial human glioblastoma multiforme xenograft. We have demonstrated that the increase in blood-tumor barrier permeability correlates with intracranial tumor size and that there is marked heterogeneity in permeability within each xenograft tumor as well as between xenograft tumors. The tumor core in the xenograft mouse model is characterized by the highest tumor permeability which inversely correlates with the distance from the tumor. The pilot study will image these mice using MRI (7T) between days 10-15 post injection of the xenograft using an MR contrast agent (ProHance) injected via a tail vein under anesthesia. Following the MRI, standard quantitative permeability measurements will be performed using 14C labeled AIB (ARC 145B-aminoisobutyric acid) in the CCIF which will validate the MR permeability data. For these pilot studies, we will use the xenograft tumor that is rapidly growing (GBM 270) and with a high blood-tumor barrier permeability. It remains unknown how the blood-tumor barrier permeability changes with increased tumor size. In addition, the ability to image the modulation of the blood-brain and blood-tumor barrier permeability has tremendous translational appeal for predicting tumor-specific drug delivery and for validating molecular vascular targeting strategies to treat brain tumors.

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