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. ? ? ?
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