Cellular MRI in Glioma and Radiation Necrosis

描述(申请人提供)：最近，使用两种FDA批准的药物，我们形成了铁氧化物-鱼精蛋白硫酸盐复合体，并标记了任何种类的哺乳动物细胞。为了检验标记细胞是否可以用作探针来检测和区分生理和/或病理情况，我们选择了胶质瘤和放射性坏死模型。据推测，体内磁性标记细胞的MR跟踪将使我们能够识别标记注入细胞的不同积聚和掺入模式，从而区分复发胶质瘤和放射性坏死。胶质瘤是一种典型的多血管中枢神经系统肿瘤。与周围正常的脑血管区域不同，多血管区域通常对造影剂具有渗透性，因此可以通过对比增强的MRI或CT检测到。然而，由于活跃的炎症反应和增加的血管通透性，放射性坏死区也可以显示出强化。因此，如果仅考虑血管通透性和/或体积的变化，则区分复发性胶质瘤和放射性坏死是有问题的。然而，一个明显的特征是，在放射性坏死的部位几乎没有活跃的血管生成。通过测定标记内皮祖细胞(EPC)在胶质瘤部位的不同迁移和掺入模式，应该可以区分放射性坏死和复发性胶质瘤。如果这被证明是可行的，使用自体标记的EPC，可以很快转化为临床试验。这些标记细胞一旦进入肿瘤或坏死区，由于细胞内氧化铁的敏感性，在体内和体外的MRI上可以检测到低信号区域。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放射性坏死区的连续磁共振成像来实现。MRI上的表现将与组织学和不同的内皮细胞标志物相关联。血管生成因子也将通过免疫组织化学方法在肿瘤内积累的内皮祖细胞或放射性坏死部位进行评估。早期发现复发或转移的胶质瘤，以及早期区分胶质瘤和放射性坏死，将有助于临床医生处理这种毁灭性的神经疾病。

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.