MR PERMEABILITY STUDIES IN A MOUSE XENOGRAFT MODEL OF GLIOBLASTOMA MULTIFORMA

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 这些动物的终末研究可以根据我们的方案进行，该方案题为“用MR显微镜绘制啮齿动物的大脑”。“，A125-04-04，2004年4月22日批准。 该方案必须进行修改以用于生存研究。 然而，据我所知，离开CCIF的动物不能被送回。 此外，作为裸鼠，它们是免疫受损的。 首先，他们可以被带到这里，在同一天成像，然后牺牲。 本研究的目的是进行体内MR渗透性研究，以评估小鼠异种移植脑肿瘤模型中BBB渗透性与肿瘤大小和肿瘤生长速率的相关性。 先天性无胸腺裸鼠将注射颅内人多形性胶质母细胞瘤异种移植物。 我们已经证明，血液肿瘤屏障通透性的增加与颅内肿瘤大小相关，并且每个异种移植肿瘤内以及异种移植肿瘤之间的通透性存在显著的异质性。异种移植小鼠模型中的肿瘤核心的特征在于最高的肿瘤渗透性，其与距肿瘤的距离负相关。 初步研究将在注射异种移植物后第10-15天使用MRI（7 T）对这些小鼠进行成像，使用MR造影剂（ProHance）在麻醉下通过尾静脉注射。MRI后，将在CCIF中使用14 C标记的AIB（ARC 145 B-氨基异丁酸）进行标准定量渗透性测量，以验证MR渗透性数据。对于这些初步研究，我们将使用快速生长的异种移植肿瘤（GBM 270）和高血肿瘤屏障渗透性。 目前尚不清楚血肿瘤屏障通透性如何随肿瘤大小的增加而变化。此外，对血脑和血肿瘤屏障渗透性的调节进行成像的能力对于预测肿瘤特异性药物递送和验证治疗脑肿瘤的分子血管靶向策略具有巨大的转化吸引力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Terminal study with these animals could be performed under our protocol entitled "Mapping the Rodent Brain with MR Microscopy.", A125-04-04 approved 04/22/04. This protocol would have to be modified for survival studies. However, as I understand, animals leaving CCIF cannot be returned. Additionally, being nude mice they are immuno-compromised. For starters, they could be brought over here and imaged the same day then sacrificed. 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.