title: Monitoring adenoviral based gene delivery in rat glioma by molecular imaging.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  EPCs can be used as vehicle to deliver adenoviral vector to glioma and also act as imaging probe at the same time.
authors.affiliation: Nadimpalli Ravi S Varma, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Nadimpalli Ravi S
authors.initials: NR
authors.lastname: Varma
authors.affiliation: Nadimpalli Ravi S Varma, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Barton
authors.affiliation: Nadimpalli Ravi S Varma, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Branislava
authors.initials: B
authors.lastname: Janic
authors.affiliation: Nadimpalli Ravi S Varma, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Adarsh
authors.initials: A
authors.lastname: Shankar
authors.affiliation: Nadimpalli Ravi S Varma, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Asm
authors.initials: A
authors.lastname: Iskander
authors.affiliation: Nadimpalli Ravi S Varma, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Meser M
authors.initials: MM
authors.lastname: Ali
authors.affiliation: Nadimpalli Ravi S Varma, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, MI 48202, United States.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Arbab
keywords: Adenovirus; Cord blood endothelial progenitor cells; Human sodium iodide symporter; Magnetic resonance imaging; Single photon emission computed tomography