Journal article
Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer
Nuclear medicine and biology, Vol.33(3), pp.391-398
2006
DOI: 10.1016/j.nucmedbio.2006.01.003
PMID: 16631088
Abstract
Noninvasive analysis of therapeutic transgene expression is important for the development of clinical translational gene therapy strategies against cancer. To image p53 and MnSOD gene transfer noninvasively, we used radiologically detectable dual-expressing adenoviral vectors with the human sodium iodide symporter (hNIS) as the reporter gene.
Dual-expressing adenoviral vectors were constructed with hNIS cloned into E3 region and therapeutic genes, either MnSOD or p53, recombined into the E1 region. Steady-state mRNA levels of hNIS were evaluated by real-time polymerase chain reaction. hNIS function was determined by iodide uptake assay and MnSOD, and p53 protein levels were assessed by Western blots.
125I
− accumulation resulting from hNIS expression in both Ad-p53-hNIS- and Ad-MnSOD-hNIS-infected MDA-MB-435 cells could be visualized clearly on phosphorimaging autoradiograph. Iodide accumulation increased with increasing adenovirus titer, and there was a linear correlation between iodide uptake and dose. p53 and MnSOD protein levels increased as a function of adenovirus titer, and there was a direct positive correlation between p53 and MnSOD expression and hNIS function. P53 and MnSOD overexpression inhibited cell growth in the dual-expressing adenoviral vector–infected cells.
Radiological detection of hNIS derived from dual-expressing adenoviral vectors is a highly effective method to monitor therapeutic gene transfer and expression in a noninvasive manner.
Details
- Title: Subtitle
- Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer
- Creators
- Gang Niu - Free Radical and Radiation Biology Program, The University of Iowa, Iowa City, IA 52242, USARichard D Anderson - ViraQuest Inc., North Liberty, IA 52317, USAMark T Madsen - Department of Radiology, The University of Iowa, Iowa City, IA 52242, USAMichael M Graham - Department of Radiology, The University of Iowa, Iowa City, IA 52242, USALarry W Oberley - Free Radical and Radiation Biology Program, The University of Iowa, Iowa City, IA 52242, USAFrederick E Domann - Free Radical and Radiation Biology Program, The University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Nuclear medicine and biology, Vol.33(3), pp.391-398
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.nucmedbio.2006.01.003
- PMID
- 16631088
- ISSN
- 0969-8051
- eISSN
- 1872-9614
- Language
- English
- Date published
- 2006
- Academic Unit
- Radiology; Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047856602771
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