IN VIVO MR PERMEABILITY IN MOUSE XENOGRAFT MODEL OF GLIOBLASTOMA MULTIFORMA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的目的是在体内进行MR通透性研究，以评估血脑屏障通透性与肿瘤大小和肿瘤生长速度的相关性。 先天无瘤裸鼠将被注射一种颅内多形性胶质母细胞瘤异种移植瘤。我们已经证明，血-肿瘤屏障通透性的增加与颅内肿瘤的大小有关，并且在每个异种移植瘤内以及异种移植瘤之间的通透性存在明显的异质性。在异种移植小鼠模型中，肿瘤核心具有最高的肿瘤渗透性，这与距离肿瘤的距离成反比。 这项初步研究将在麻醉下通过尾静脉注射磁共振造影剂(ProHance)，在注射异种移植物后的10-15天内，使用MRI(7T)对这些小鼠进行成像。磁共振成像后，将在CCIF中使用14C标记的AIB(ARC 145B-氨基异丁酸)进行标准的定量渗透性测量，以验证MR渗透性数据。对于这些先导性研究，我们将使用快速生长的异种移植瘤(GBM 270)，并具有较高的血-肿瘤屏障渗透性。 目前尚不清楚血-肿瘤屏障通透性如何随着肿瘤大小的增加而变化。此外，成像血-脑和血-肿瘤屏障通透性变化的能力对于预测肿瘤特异性药物输送和验证治疗脑肿瘤的分子血管靶向策略具有巨大的翻译吸引力。

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.