IN VIVO MR PERMEABILITY IN MOUSE XENOGRAFT MODEL OF GLIOBLASTOMA MULTIFORMA

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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的渗透性如何随着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. 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.