MR PERMEABILITY STUDIES IN A MOUSE XENOGRAFT MODEL OF GLIOBLASTOMA MULTIFORMA

多形性胶质母细胞瘤小鼠异种移植模型的 MR 通透性研究

• 批准号: 8363227
• 负责人: Gerald Arthur Grant
• 金额: $ 1.23万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363227
• 关键词: A Mouse; Aminoisobutyric Acids; Anesthesia procedures; Animals; Blood; Blood Vessels; Brain; Brain Neoplasms; Contrast Media; Data; Drug Delivery Systems; Funding; Glioblastoma; Goals; Grant; Heterogeneity; Human; Image; Injection of therapeutic agent; Intracranial Neoplasms; Label; Left; Magnetic Resonance Imaging; Maps; Measurement; Microscopy; Modeling; Molecular; Mus; National Center for Research Resources; Nude Mice; Permeability; Pilot Projects; Principal Investigator; Prohance; Protocols documentation; Research; Research Infrastructure; Resources; Rodent; Source; Tail; United States National Institutes of Health; Veins; Xenograft Model; Xenograft procedure; cost; in vivo; mouse model; 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. 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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 对这些动物的终末研究可以根据我们的方案进行，名为“用MR显微镜绘制啮齿类动物的大脑图”，A125-04-04批准04/22/04。为了进行生存研究，必须对这一方案进行修改。然而，据我所知，离开CCIF的动物不能退还。此外，作为裸鼠，它们的免疫功能受到了损害。首先，它们可以被带到这里，在同一天被成像，然后被牺牲。 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。