Cellular MRI in Glioma and Radiation Necrosis

描述（由申请人提供）：最近，使用两种FDA批准的试剂，我们形成ferumoxides-硫酸鱼精蛋白复合物并标记任何种类的哺乳动物细胞。为了检查标记的细胞是否可以用作探针来检测和区分生理和/或病理条件，我们选择了胶质瘤和放射性坏死模型。据推测，磁标记细胞的体内MR跟踪将使我们能够识别标记的注射细胞的积累和掺入的不同模式，从而允许复发性胶质瘤和放射性坏死之间的分化。神经胶质瘤是一种中枢神经系统肿瘤，通常表现为血供过多。与脑血管系统的周围正常区域不同，血管过多区域通常可渗透造影剂，因此可以通过对比增强MRI或CT检测到。然而，由于活跃的炎症反应和血管通透性增加，放射性坏死区域也可以显示增强。因此，如果仅考虑血管通透性和/或体积的变化，则将复发性胶质瘤与放射性坏死区分开来是有问题的。然而，一个显著的特征是在放射性坏死部位几乎没有活跃的血管生成。通过测定胶质瘤部位标记的内皮祖细胞（EPCs）的迁移和掺入模式，有可能区分放射性坏死和复发性胶质瘤。如果这被证明是可行的，那么使用自体标记的EPCs可以很快转化为临床试验。这些标记的细胞一旦掺入肿瘤或坏死区域，由于细胞内氧化铁的易感性效应，可以在体内和离体MRI上检测到低信号强度区域。这些目标将通过在不同时间点注射标记细胞后获得肿瘤和辐射坏死区域的系列MRI来实现。MRI表现与组织学及内皮细胞标志物相关。还将通过免疫组织化学在肿瘤或放射性坏死中积聚的EPC部位评估血管生成因子。早期发现复发或转移的胶质瘤，以及早期鉴别胶质瘤与放射性坏死，将有助于临床治疗这一毁灭性的神经系统疾病。

DESCRIPTION (provided by applicant): Recently, using two FDA-approved agents, we formed ferumoxides-protamine sulfate complex and labeled any kind of mammalian cells. To examine whether labeled cells can be used as probes to detect and differentiate physiological and/or pathological conditions, we have selected glioma and radiation necrosis models. It is hypothesized that in vivo MR tracking of magnetically labeled cells will enable us to identify different patterns of accumulation and incorporation of labeled injected cells, thus allowing for differentiation between recurrent glioma and radiation necrosis. Glioma is a central nervous system neoplasm that typically shows hypervascularity. Unlike the surrounding normal regions of cerebral vasculature, areas of hypervascularity are typically permeable to contrast agents, and can thus be detected by contrast-enhanced MRI or CT. However, areas of radiation necrosis can also show enhancement due to active inflammatory reactions and increasing vascular permeability. Thus, distinguishing recurrent glioma from radiation necrosis becomes problematic if only changes in vascular permeability and/or volume are considered. One distinguishing characteristic, however, is that there is little active angiogenesis at the site of radiation necrosis. By determining the differential migration and incorporation patterns of labeled endothelial progenitor cells (EPCs) at the site of glioma, it should be possible to differentiate between radiation necrosis and recurrent glioma. If this proves feasible, a translation into clinical trials can quickly follow, employing autologous labeled EPCs. These labeled cells, once incorporated into the tumors or areas of necrosis, can be detected as low signal intensity areas on in vivo and ex vivo MRI because of the susceptibility effects of iron oxides inside the cells. These objectives will be achieved by obtaining serial MRI of tumors and radiation necrotic areas after injecting labeled cells at different time points. The findings on MRI will be correlated with histology and different markers of endothelial cells. Angiogenic factors will also be assessed by immunohistochemistry at the site of accumulated EPCs in tumors or radaition necrosis. Early detection of recurrent or metastatic glioma as well as early differentiation of glioma from radiation necrosis will help clinician to tackle the devastating neurological disease.