Monitoring adenoviral based gene delivery in rat glioma by molecular imaging  

作　　者：Nadimpalli Ravi S Varma Kenneth N Barton Branislava Janic Adarsh Shankar ASM Iskander Meser M Ali Ali S Arbab 

机构地区：[1]Cellular and Molecular Imaging Laboratory,Department of Radiology,Henry Ford Hospital,Detroit,MI 48202,United States [2]Department of Radiation Oncology,Henry Ford Hospital,Detroit,MI 48202,United States

出　　处：《World Journal of Clinical Oncology》2013年第4期91-101,共11页世界临床肿瘤学杂志（英文版）

基　　金：Supported by NIH Grants 1R21CA129801(to Arbab AS);R01CA122031(to Arbab AS)

摘　　要：AIM:To determine whether endothelial progenitor cells(EPCs)can be used as delivery vehicle for adenoviral vectors and imaging probes for gene therapy in glioblastoma.METHODS:To use cord blood derived EPCs as delivery vehicle for adenoviral vectors and imaging probes for glioma gene therapy,a rat model of human glioma was made by implanting U251 cells orthotopically.EPCs were transfected with an adenovirus(AD5/carrying hNIS gene)and labeled with iron oxide and inoculated them directly into the tumor 14 d following implantation of U251 cells.Magnetic resonance imaging(MRI)was used to in vivo track the migration of EPCs in the tumor.The expression of gene products was determined by in vivo Tc-99m single photon emission computed tomography(SPECT).The findings were validated with immunohistochemistry(IHC).RESULTS:EPCs were successfully transfected with the adenoviral vectors carrying hNIS which was proved by significantly(P<0.05)higher uptake of Tc-99m in transfected cells.Viability of EPCs following transfection and iron labeling was not altered.In vivo imaging showed the presence of iron positive cells and the expression of transgene(hNIS)product on MRI and SPECT,respectively,all over the tumors following administration of transfected and iron labeled EPCs in the tumors.IHC confirmed the distribution of EPC around the tumor away from the injection site and also showed transgene expression in the tumor.The results indicated the EPCs’ability to deliver adenoviral vectors into the glioma upon intratumor injection.CONCLUSION:EPCs can be used as vehicle to deliver adenoviral vector to glioma and also act as imaging probe at the same time.AIM: To determine whether endothelial progenitor cells(EPCs) can be used as delivery vehicle for adenoviral vectors and imaging probes for gene therapy in glioblastoma.METHODS: To use cord blood derived EPCs as delivery vehicle for adenoviral vectors and imaging probes for glioma gene therapy, a rat model of human glioma was made by implanting U251 cells orthotopically. EPCs were transfected with an adenovirus(AD5/carrying h NIS gene) and labeled with iron oxide and inoculated them directly into the tumor 14 d following implantationof U251 cells. Magnetic resonance imaging(MRI) was used to in vivo track the migration of EPCs in the tumor. The expression of gene products was determined by in vivo Tc-99 m single photon emission computed tomography(SPECT). The findings were validated with immunohistochemistry(IHC). RESULTS: EPCs were successfully transfected with the adenoviral vectors carrying h NIS which was proved by significantly(P < 0.05) higher uptake of Tc-99 m in transfected cells. Viability of EPCs following transfection and iron labeling was not altered. In vivo imaging showed the presence of iron positive cells and the expression of transgene(h NIS) product on MRI and SPECT, respectively, all over the tumors following administration of transfected and iron labeled EPCs in the tumors. IHC confirmed the distribution of EPC around the tumor away from the injection site and also showed transgene expression in the tumor. The results indicated the EPCs’ ability to deliver adenoviral vectors into the glioma upon intratumor injection.CONCLUSION: EPCs can be used as vehicle to deliver adenoviral vector to glioma and also act as imaging probe at the same time.

关 键 词：Cord blood endothelial PROGENITOR cells ADENOVIRUS Human sodium IODIDE SYMPORTER Single photon emission computed tomography Magnetic resonance imaging 

分 类 号：R739.41[医药卫生—肿瘤]