Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer

Nuclear Medicine and Biology
Gang NiuFrederick E Domann

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 ...Continue Reading

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Citations

Jun 13, 2008·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Talakad Goolaiah LohithYasuhisa Fujibayashi
Mar 1, 2008·Regenerative Medicine·Ali S Arbab, Joseph A Frank
Aug 20, 2015·The Journal of Endocrinology·Vikki L Poole, Christopher J McCabe
Aug 27, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tanja HakkarainenAkseli Hemminki
Aug 16, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Seung-Yoon ParkIn-San Kim

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