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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA122031-02
Application #
7493533
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Zhang, Huiming
Project Start
2007-09-07
Project End
2011-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
2
Fiscal Year
2008
Total Cost
$247,950
Indirect Cost
Name
Henry Ford Health System
Department
Type
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Shankar, Adarsh; Kumar, Sanath; Iskander, A S M et al. (2014) Subcurative radiation significantly increases cell proliferation, invasion, and migration of primary glioblastoma multiforme in vivo. Chin J Cancer 33:148-58
Chwang, Wilson B; Jain, Rajan; Bagher-Ebadian, Hassan et al. (2014) Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE-MRI nested model selection. J Magn Reson Imaging 40:1223-9
Varma, Nadimpalli Ravi S; Shankar, Adarsh; Iskander, Asm et al. (2013) Differential biodistribution of intravenously administered endothelial progenitor and cytotoxic T-cells in rat bearing orthotopic human glioma. BMC Med Imaging 13:17
Varma, Nadimpalli Ravi S; Barton, Kenneth N; Janic, Branislava et al. (2013) Monitoring adenoviral based gene delivery in rat glioma by molecular imaging. World J Clin Oncol 4:91-101
Iskander, Asm; Knight, Robert A; Zhang, Zheng Gang et al. (2013) Intravenous administration of human umbilical cord blood-derived AC133+ endothelial progenitor cells in rat stroke model reduces infarct volume: magnetic resonance imaging and histological findings. Stem Cells Transl Med 2:703-14
Isozaki, Takeo; Arbab, Ali S; Haas, Christian S et al. (2013) Evidence that CXCL16 is a potent mediator of angiogenesis and is involved in endothelial progenitor cell chemotaxis : studies in mice with K/BxN serum-induced arthritis. Arthritis Rheum 65:1736-46
Kumar, Sanath; Arbab, Ali S; Jain, Rajan et al. (2012) Development of a novel animal model to differentiate radiation necrosis from tumor recurrence. J Neurooncol 108:411-20
Liu, Yongbo; Gao, Xiaohua; Deeb, Dorrah et al. (2012) Anticancer agent xanthohumol inhibits IL-2 induced signaling pathways involved in T cell proliferation. J Exp Ther Oncol 10:1-8
Janic, Branislava; Jafari-Khouzani, Kourosh; Babajani-Feremi, Abbas et al. (2012) MRI tracking of FePro labeled fresh and cryopreserved long term in vitro expanded human cord blood AC133+ endothelial progenitor cells in rat glioma. PLoS One 7:e37577
Arbab, Ali S (2012) Activation of alternative pathways of angiogenesis and involvement of stem cells following anti-angiogenesis treatment in glioma. Histol Histopathol 27:549-57

Showing the most recent 10 out of 36 publications