Original Article
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World J Clin Oncol. Nov 10, 2013; 4(4): 91-101
Published online Nov 10, 2013. doi: 10.5306/wjco.v4.i4.91
Monitoring adenoviral based gene delivery in rat glioma by molecular imaging
Nadimpalli Ravi S Varma, Kenneth N Barton, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab
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
Kenneth N Barton, Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI 48202, United States
Author contributions: Varma NRS and Arbab AS carried out the experimental design, data analysis; Varma NRS carried out the experiments (tumour model development, infections, cell labelling, SPECT imaging) and manuscript writing; Varma NRS, Ali MM and Arbab AS performed the MRI imaging and analysis; Varma NRS, Iskander ASM and Shankar A carried out histological staining and analysis; Barton KN carried out design of viral vectors; Varma NRS and Janic B carried out viral production; Arbab AS carried out the SPECT and MRI image analysis; all authors read and approved the final manuscript.
Supported by NIH Grants 1R21CA129801 (to Arbab AS); R01CA122031 (to Arbab AS)
Correspondence to: Nadimpalli Ravi S Varma, PhD, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, 1 Ford place, 2F, Box 82, Detroit, MI 48202, United States. ravin@rad.hfh.edu
Telephone: +1-313-8744349 Fax: +1-313-8744494
Received: February 22, 2013
Revised: May 21, 2013
Accepted: July 9, 2013
Published online: November 10, 2013
Abstract

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.

Keywords: Cord blood endothelial progenitor cells, Adenovirus, Human sodium iodide symporter, Single photon emission computed tomography, Magnetic resonance imaging

Core tip: Endothelial progenitor cells (EPCs) can be transfected with replication competent adenoviral vector carrying therapeutic/reporter gene and the transfected EPCs can be used to deliver the gene in tumor gene therapy. EPCs can be used as both imaging and therapeutic probes.